Cimetidine

Identification

Summary

Cimetidine is a histamine H2 receptor antagonist used to manage GERD, peptic ulcer disease, and indigestion.

Brand Names
Good Sense Heartburn Relief, Tagamet
Generic Name
Cimetidine
DrugBank Accession Number
DB00501
Background

A histamine congener, it competitively inhibits histamine binding to histamine H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrins output. It also blocks the activity of cytochrome P-450 which might explain proposals for use in neoadjuvant therapy.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 252.339
Monoisotopic: 252.115715232
Chemical Formula
C10H16N6S
Synonyms
  • 1-Cyano-2-methyl-3-(2-(((5-methyl-4-imidazolyl)methyl)thio)ethyl)guanidine
  • 2-cyano-1-methyl-3-(2-(((5-methylimidazol-4-yl)methyl)thio)ethyl)guanidine
  • Cimetidin
  • Cimetidina
  • Cimétidine
  • Cimetidine
  • Cimetidinum
  • N-cyano-N'-methyl-N''-(2-([(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl)ethyl)guanidine
  • N''-cyano-N-methyl-N'-(2-{[(5-methyl-1H-imidazol-4-yl)methyl]thio}ethyl)guanidine
External IDs
  • NSC-335308
  • SKF 92334
  • SKF-92334

Pharmacology

Indication

Cimetidine is indicated to reduce gastric acid secretion and to treat the following disease states: duodenal ulcers, non-malignant gastric ulcers, gastroesophageal reflux disease, and pathological hypersecretion associated with Zollinger-Ellison Syndrome, systemic mastocytosis, and multiple endocrine adenomas.7 It is indicated for prophylaxis of recurrent gastric or duodenal ulcers, as adjunctive therapy in the management of cystic fibrosis in children, and to treat NSAID induced lesions and gastrointestinal symptoms.7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in management ofCystic fibrosis (cf)••••••••••••••••••••••••••
Management ofGerd••••••••••••••••••
Prevention ofGastrointestinal symptoms••••••••••••••••••
Treatment ofGastrointestinal symptoms••••••••••••••••••
Prevention ofHeartburn••• •••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Cimetidine is a histamine H2-receptor antagonist. It reduces basal and nocturnal gastric acid secretion and a reduction in gastric volume, acidity, and amount of gastric acid released in response to stimuli including food, caffeine, insulin, betazole, or pentagastrin. It is used to treat gastrointestinal disorders such as gastric or duodenal ulcer, gastroesophageal reflux disease, and pathological hypersecretory conditions. Cimetidine inhibits many of the isoenzymes of the hepatic CYP450 enzyme system. Other actions of Cimetidine include an increase in gastric bacterial flora such as nitrate-reducing organisms.

Mechanism of action

Cimetidine binds to an H2-receptor located on the basolateral membrane of the gastric parietal cell, blocking histamine effects. This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity.

TargetActionsOrganism
AHistamine H2 receptor
antagonist
Humans
Absorption

Two peak plasma concentrations are often observed after oral administration of cimetidine, likely as a result of discontinuous absorption in the gastrointestinal tract.6 In healthy patients, the absolute bioavailability of cimetidine is approximately 60%; however, the bioavailability can be as high as 70% in patients with peptic ulcer disease.6 Overall, rates of bioavailability are much more variable in patients with peptic ulcer disease.6

Volume of distribution

The volume of distribution of cimetidine is reported to be 1 L/kg.6

Protein binding

In humans, approximately 22.5% of cimetidine is plasma protein bound.7

Metabolism

After intravenous administration of cimetidine, the majority of the parent drug (58-77%) is eliminated unchanged in the urine.2,7 Cimetidine’s primary metabolite is cimetidine sulfoxide and represents an estimated 10-15% of total elimination.2,6 Researchers have also identified a minor cimetidine metabolite with a hydroxylated methyl group on the imidazole ring which represents only 4% of total elimination.2,6 Both cytochrome P450 enzymes and flavin-containing monooxygenases are implicated in the metabolism of cimetidine, although it is unclear which specific enzymes are involved.3 Cimetidine is a well known enzyme inhibitor and may impair the metabolism of certain co-administered medications.4

Hover over products below to view reaction partners

Route of elimination

Cimetidine is excreted primarily in the urine.7

Half-life

Cimetidine's half-life is estimated to be around 2 hours.7

Clearance

Cimetidine's reported systemic clearance value is approximately 500-600 ml/min.6

Adverse Effects
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Toxicity

In the rare event of cimetidine overdose, it is vital to maintain the airway and cardiovascular status.5 The patient should be closely monitored and provided with symptomatic and supportive treatment as needed.5 Interventions such as gastric lavage and administration of activated charcoal may be initiated if deemed appropriate and necessary.5

Pathways
PathwayCategory
Cimetidine Action PathwayDrug action
Cimetidine Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirCimetidine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Cimetidine.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Cimetidine.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Cimetidine.
AcamprosateThe excretion of Acamprosate can be decreased when combined with Cimetidine.
Food Interactions
  • Take with food. Food increases bioavailability. For prophylaxis of gastric symptoms, take cimetidine 30-60 minutes prior to food administration.

Products

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dosage, form, labeller, route of administration, and marketing period.
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Product Ingredients
IngredientUNIICASInChI Key
Cimetidine hydrochlorideWF1049167370059-30-2QJHCNBWLPSXHBL-UHFFFAOYSA-N
Product Images
International/Other Brands
Cimetag (Julphar) / Tagamet HB 200 (GlaxoSmithKline) / Tagamet HB200 (GlaxoSmithKline) / Ulcedine / Ulcerfen (Finadiet) / Ulcimet (Farmasa)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CimetidineTablet200 mgOralAa Pharma Inc1982-12-31Not applicableCanada flag
CimetidineTablet800 mgOralAa Pharma Inc1988-12-31Not applicableCanada flag
CimetidineTablet600 mgOralAa Pharma Inc1983-12-31Not applicableCanada flag
CimetidineTablet, film coated200 mg/1OralTEVA PHARMACEUTICALS USA2006-11-282006-11-28US flag
CimetidineTablet400 mgOralAa Pharma Inc1983-12-31Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-cimetidine Oral SolutionLiquid300 mg / 5 mLOralApotex Corporation2001-01-05Not applicableCanada flag
CimetidineTablet, film coated400 mg/1Oralbryant ranch prepack2004-02-02Not applicableUS flag
CimetidineTablet, film coated200 mg/1OralMylan Pharmaceuticals Inc.1994-05-17Not applicableUS flag
CimetidineTablet400 mg/1OralRebel Distributors2010-11-24Not applicableUS flag
CimetidineSolution300 mg/5mLOralPharmaceutical Associates, Inc.2021-02-122023-04-28US flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Acid ReducerTablet, film coated200 mg/1OralKroger Company2015-10-21Not applicableUS flag
Acid ReducerTablet200 mg/1OralRite Aid2005-07-082014-07-27US flag
Basic Care Acid ReducerTablet, film coated200 mg/1OralAmazon.com Services LLC2022-01-09Not applicableUS flag
Cimetidine Acid ReducerTablet, film coated200 mg/1OralWalgreen Company2001-03-27Not applicableUS flag
DG Health Heartburn ReliefTablet200 mg/1OralDolgencorp2010-03-022014-08-18US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Cimetidine 10% / Lidocaine 5% / Salicylic Acid 40%Cimetidine (10 g/100g) + Lidocaine (5 g/100g) + Salicylic acid (40 g/100g)CreamTopicalSincerus Florida, LLC2019-05-01Not applicableUS flag
Cimetidine 5% / Ibuprofen 2% / Salicylic Acid 17%Cimetidine (5 g/100g) + Ibuprofen (2 g/100g) + Salicylic acid (17 g/100g)GelTopicalSincerus Florida, LLC2019-05-17Not applicableUS flag

Categories

ATC Codes
A02BA51 — Cimetidine, combinationsA02BA01 — Cimetidine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as imidazoles. These are compounds containing an imidazole ring, which is an aromatic five-member ring with two nitrogen atoms at positions 1 and 3, and three carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Imidazoles
Direct Parent
Imidazoles
Alternative Parents
Heteroaromatic compounds / Guanidines / Sulfenyl compounds / Propargyl-type 1,3-dipolar organic compounds / Dialkylthioethers / Carboximidamides / Azacyclic compounds / Organopnictogen compounds / Imines / Hydrocarbon derivatives
Substituents
Aromatic heteromonocyclic compound / Azacycle / Carboximidamide / Dialkylthioether / Guanidine / Heteroaromatic compound / Hydrocarbon derivative / Imidazole / Imine / Organic 1,3-dipolar compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles, guanidines, aliphatic sulfide, nitrile (CHEBI:3699)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
80061L1WGD
CAS number
51481-61-9
InChI Key
AQIXAKUUQRKLND-UHFFFAOYSA-N
InChI
InChI=1S/C10H16N6S/c1-8-9(16-7-15-8)5-17-4-3-13-10(12-2)14-6-11/h7H,3-5H2,1-2H3,(H,15,16)(H2,12,13,14)
IUPAC Name
(Z)-N''-cyano-N-methyl-N'-(2-{[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl}ethyl)guanidine
SMILES
CN\C(NCCSCC1=C(C)NC=N1)=N\C#N

References

Synthesis Reference

Saburo Uchikuga, Tomoyasu Tashiro, Yasuko Osawa, "Process for preparing the H.sub.2 -receptor antagonist cimetidine." U.S. Patent US4413129, issued March, 1972.

US4413129
General References
  1. Michnovicz JJ, Galbraith RA: Cimetidine inhibits catechol estrogen metabolism in women. Metabolism. 1991 Feb;40(2):170-4. [Article]
  2. Larsson R, Erlanson P, Bodemar G, Walan A, Bertler A, Fransson L, Norlander B: The pharmacokinetics of cimetidine and its sulphoxide metabolite in patients with normal and impaired renal function. Br J Clin Pharmacol. 1982 Feb;13(2):163-70. doi: 10.1111/j.1365-2125.1982.tb01351.x. [Article]
  3. Lu X, Li C, Fleisher D: Cimetidine sulfoxidation in small intestinal microsomes. Drug Metab Dispos. 1998 Sep;26(9):940-2. [Article]
  4. Hoensch HP, Hutzel H, Kirch W, Ohnhaus EE: Isolation of human hepatic microsomes and their inhibition by cimetidine and ranitidine. Eur J Clin Pharmacol. 1985;29(2):199-206. doi: 10.1007/BF00547422. [Article]
  5. Pino MA, Azer SA: Cimetidine . [Article]
  6. Somogyi A, Gugler R: Clinical pharmacokinetics of cimetidine. Clin Pharmacokinet. 1983 Nov-Dec;8(6):463-95. doi: 10.2165/00003088-198308060-00001. [Article]
  7. DPD Approved Drug Products: Cimetidine (200, 300, 400, 600, 800 mg) [Link]
Human Metabolome Database
HMDB0014644
KEGG Drug
D00295
KEGG Compound
C06952
PubChem Compound
2756
PubChem Substance
46505360
ChemSpider
2654
BindingDB
181119
RxNav
2541
ChEBI
3699
ChEMBL
CHEMBL30
ZINC
ZINC000018115268
Therapeutic Targets Database
DAP000338
PharmGKB
PA449001
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cimetidine
MSDS
Download (73.4 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableCommunity Acquired Pneumonia (CAP) / Gastro-esophageal Reflux Disease (GERD)1somestatusstop reasonjust information to hide
Not AvailableCompletedDiagnosticKidney Transplantation1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1somestatusstop reasonjust information to hide
4CompletedBasic ScienceHealthy Volunteers (HV)1somestatusstop reasonjust information to hide
4CompletedPreventionAspiration of Gastric Contents1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
  • Apotex inc
  • Contract pharmacal corp
  • Dava pharmaceuticals inc
  • Endo pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lek pharmaceuticals d d
  • Mylan pharmaceuticals inc
  • L perrigo co
  • Perrigo co
  • Pliva inc
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Hospira inc
  • Luitpold pharmaceuticals inc
  • Teva parenteral medicines inc
  • Actavis mid atlantic llc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Hi tech pharmacal co inc
  • Novex pharma
  • Pharmaceutical assoc inc div beach products
  • Teva pharmaceuticals usa
  • Wockhardt eu operations (swiss) ag
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotex Inc.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Baxter International Inc.
  • Bristol-Myers Squibb Co.
  • Bryant Ranch Prepack
  • Cardinal Health
  • Central Texas Community Health Centers
  • Comprehensive Consultant Services Inc.
  • Darby Dental Supply Co. Inc.
  • DAVA Pharmaceuticals
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Endo Pharmaceuticals Inc.
  • GlaxoSmithKline Inc.
  • Group Health Cooperative
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hi Tech Pharmacal Co. Inc.
  • Hospira Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Lek Pharmaceuticals Inc.
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novex Pharma
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Perrigo Co.
  • Pharma Pac LLC
  • Pharmaceutical Association
  • Pharmedix
  • Pharmpak Inc.
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescription Dispensing Service Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Sandhills Packaging Inc.
  • Sanofi-Aventis Inc.
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Va Cmop Dallas
  • Wockhardt Ltd.
Dosage Forms
FormRouteStrength
SuspensionOral200 MG/5ML
SolutionParenteral300.000 mg
TabletOral400.000 mg
Tablet, film coatedOral800 mg
Tablet, coatedOral
Tablet, effervescent200 MG
Tablet, coatedOral800 MG
SolutionOral400 mg/6.67mL
TabletOral
TabletOral300 mg/1
TabletOral300 mg
TabletOral400 mg/1
TabletOral600 mg
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral300 mg/1
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral800 mg/1
CreamTopical
Tablet, film coatedOral400.00 mg
GelTopical
Injection, solutionIntramuscular; Intravenous150 mg/1mL
SolutionOral300 mg/5mL
Injection, solutionIntravenous6 mg/1mL
TabletOral200 mg / tab
TabletOral800 mg / tab
InjectionIntravenous
Tablet, effervescentOral200 MG
Tablet, effervescent
Syrup
TabletOral100 mg
TabletOral200 mg/1
SolutionIntramuscular; Intravenous150 mg / mL
Tablet, film coatedOral
InjectionIntramuscular; Intravenous150 mg/ml
Tablet, soluble
Granule, for suspensionOral
Injection, solution
Tablet, delayed releaseOral800 mg
LiquidIntravenous6 mg / mL
LiquidIntramuscular; Intravenous150 mg / mL
LiquidOral300 mg / 5 mL
LiquidOral60 mg / mL
Pill
Powder
Capsule
Granule, for solutionOral
Granule, for solutionOral800 mg
InjectionIntramuscular
TabletOral800 mg
TabletOral200 mg
Solution150 mg/1ml
Tablet, coatedOral400 mg
Tablet, coatedOral200 mg
TabletOral400 mg
Capsule200 mg
SuspensionOral50 mg/5mL
Tablet, film coatedOral200 mg
Tablet, film coatedOral400 mg
Solution100 mg/1ml
Prices
Unit descriptionCostUnit
Cimetidine 800 mg tablet2.7USD tablet
Tagamet 400 mg tablet2.51USD tablet
Cimetidine 150 mg/ml vial1.67USD ml
Cimetidine powder1.48USD g
Cimetidine 400 mg tablet1.44USD tablet
Tagamet 300 mg tablet1.28USD tablet
Cimetidine 300 mg tablet0.93USD tablet
Cimetidine 200 mg tablet0.46USD tablet
Cimetidine HCl 300 mg/5ml Solution0.38USD ml
Tagamet hb 200 mg tablet0.37USD tablet
Apo-Cimetidine 800 mg Tablet0.27USD tablet
Mylan-Cimetidine 800 mg Tablet0.27USD tablet
Acid reducer 200 mg tablet0.21USD tablet
Apo-Cimetidine 600 mg Tablet0.18USD tablet
Mylan-Cimetidine 600 mg Tablet0.18USD tablet
Novo-Cimetine 600 mg Tablet0.18USD tablet
Nu-Cimet 600 mg Tablet0.18USD tablet
Apo-Cimetidine 400 mg Tablet0.14USD tablet
Mylan-Cimetidine 400 mg Tablet0.14USD tablet
Novo-Cimetine 400 mg Tablet0.14USD tablet
Nu-Cimet 400 mg Tablet0.14USD tablet
Apo-Cimetidine 200 mg Tablet0.09USD tablet
Apo-Cimetidine 300 mg Tablet0.09USD tablet
Mylan-Cimetidine 300 mg Tablet0.09USD tablet
Novo-Cimetine 300 mg Tablet0.09USD tablet
Nu-Cimet 300 mg Tablet0.09USD tablet
Heartburn relief 200 mg tablet0.08USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)142 °CPhysProp
water solubility9380 mg/L (at 25 °C)MCFARLAND,JW ET AL. (2001)
logP0.40HANSCH,C ET AL. (1995)
logS-1.35ADME Research, USCD
Caco2 permeability-5.89ADME Research, USCD
pKa6.8TOMLINSON,E & HAFKENSCHEID,TL (1986)
Predicted Properties
PropertyValueSource
logP-0.11Chemaxon
pKa (Strongest Acidic)13.38Chemaxon
pKa (Strongest Basic)6.91Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area88.89 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity70.32 m3·mol-1Chemaxon
Polarizability27.28 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9855
Blood Brain Barrier-0.6782
Caco-2 permeable-0.6358
P-glycoprotein substrateSubstrate0.7887
P-glycoprotein inhibitor INon-inhibitor0.8781
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterInhibitor0.7233
CYP450 2C9 substrateNon-substrate0.8048
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5795
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.5773
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9575
Ames testNon AMES toxic0.837
CarcinogenicityNon-carcinogens0.9579
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.7341 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7983
hERG inhibition (predictor II)Non-inhibitor0.8745
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (10 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0005-9500000000-8ff5fa28797a788c95be
Mass Spectrum (Electron Ionization)MSsplash10-002b-9510000000-36ce01132725fd5bf5d8
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0002-9511000000-75fc9243ad1eb9c79cb4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4j-5900000000-122f9dbdf583bbe3dee8
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0002-9300000000-39ee157d9e264867cfa4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0002-9000000000-6e876a668444c8277412
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0002-9000000000-85640be9b2799889fd02
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0002-9000000000-9b8d3eafde213bee6396
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4j-9000000000-b47e11697992a843f5e4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-9000000000-75ebe86c90f5ed341c57
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0aor-9000000000-d7302885bef7454b4db2
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-9000000000-b2f3ab1b5ae1e2f8f8bb
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-0930000000-dbae8348b5c999cc664d
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-052b-9600000000-8b4b94cd7303c9b9a0ef
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0002-9000000000-c23b62afdf4dff8c43db
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0002-9000000000-e477cd71a628f6adaf46
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-052e-9000000000-61584ad991262d50a01b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0zfr-1980000000-84e04b032e6f422e5b6b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0aos-2900000000-e8d9297512335ce612fb
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-052b-9800000000-7235208cf21d7ea1f7ad
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9300000000-4996f6630fe29fccd7d1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9100000000-a5e040b5d19e189571ba
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9000000000-d8853f62b77fc7f6ab01
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9000000000-a5bdbde532dc871c2dc3
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-114j-9000000000-89e11e4ab1dbea690ecd
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-1000-9000000000-2968f2af0b540684c21f
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-0090000000-b6ea3493555e798b637d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0aos-2910000000-c696b6aba5edd10fe848
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00kb-9700000000-6b130a82094066468edc
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-9200000000-6f64d37f41bf3bddd538
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-9100000000-f23125855effae49cbd8
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0aor-0900000000-9d38315a88e4b11bc9e7
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0pb9-2940000000-eb44b45cbe2d97c7791c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-9511000000-75fc9243ad1eb9c79cb4
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-2590000000-d4426c98ddeb68548584
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9210000000-4ca986ea71be6573fff1
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014m-8920000000-401495365da550ba4529
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014l-9100000000-b4cf504e861d263f6796
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-9420000000-11bda88f2bdb0a982fc6
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-10538fd91e4552d87b18
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0zfr-2790000000-b809396e67a091a93a2c
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-9100000000-510728b470acefca781a
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-066s-5910000000-f9314982f660458c4cda
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-9100000000-f39fdef3e431b2ab4323
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0005-9210000000-7a414fc96efc20551288
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00kf-9000000000-f820d527212dc13b2d2b
1H NMR Spectrum1D NMRNot Applicable
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-165.4053447
predicted
DarkChem Lite v0.1.0
[M-H]-165.8625447
predicted
DarkChem Lite v0.1.0
[M-H]-154.96318
predicted
DeepCCS 1.0 (2019)
[M-H]-165.4053447
predicted
DarkChem Lite v0.1.0
[M-H]-165.8625447
predicted
DarkChem Lite v0.1.0
[M-H]-165.4053447
predicted
DarkChem Lite v0.1.0
[M-H]-165.8625447
predicted
DarkChem Lite v0.1.0
[M-H]-154.96318
predicted
DeepCCS 1.0 (2019)
[M-H]-154.96318
predicted
DeepCCS 1.0 (2019)
[M+H]+166.5714447
predicted
DarkChem Lite v0.1.0
[M+H]+166.9122447
predicted
DarkChem Lite v0.1.0
[M+H]+157.32118
predicted
DeepCCS 1.0 (2019)
[M+H]+166.5714447
predicted
DarkChem Lite v0.1.0
[M+H]+166.9122447
predicted
DarkChem Lite v0.1.0
[M+H]+166.5714447
predicted
DarkChem Lite v0.1.0
[M+H]+166.9122447
predicted
DarkChem Lite v0.1.0
[M+H]+157.32118
predicted
DeepCCS 1.0 (2019)
[M+H]+157.32118
predicted
DeepCCS 1.0 (2019)
[M+Na]+166.2492447
predicted
DarkChem Lite v0.1.0
[M+Na]+166.3485447
predicted
DarkChem Lite v0.1.0
[M+Na]+164.62956
predicted
DeepCCS 1.0 (2019)
[M+Na]+166.2492447
predicted
DarkChem Lite v0.1.0
[M+Na]+166.3485447
predicted
DarkChem Lite v0.1.0
[M+Na]+166.2492447
predicted
DarkChem Lite v0.1.0
[M+Na]+166.3485447
predicted
DarkChem Lite v0.1.0
[M+Na]+164.62956
predicted
DeepCCS 1.0 (2019)
[M+Na]+164.62956
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway (By similarity)
Specific Function
G protein-coupled serotonin receptor activity
Gene Name
HRH2
Uniprot ID
P25021
Uniprot Name
Histamine H2 receptor
Molecular Weight
40097.65 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Hernandez-Munoz R, Montiel-Ruiz C, Vazquez-Martinez O: Gastric mucosal cell proliferation in ethanol-induced chronic mucosal injury is related to oxidative stress and lipid peroxidation in rats. Lab Invest. 2000 Aug;80(8):1161-9. [Article]
  3. Kuint J, Linder N, Reichman B: Hypoxemia associated with cimetidine therapy in a newborn infant. Am J Perinatol. 1996 Jul;13(5):301-3. [Article]
  4. Takahashi HK, Watanabe T, Yokoyama A, Iwagaki H, Yoshino T, Tanaka N, Nishibori M: Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes. Mol Pharmacol. 2006 Aug;70(2):450-3. Epub 2006 May 24. [Article]
  5. Pino MA, Azer SA: Cimetidine . [Article]
  6. Duda D, Lorenz W, Celik I: Histamine release in mesenteric traction syndrome during abdominal aortic aneurysm surgery: prophylaxis with H1 and H2 antihistamines. Inflamm Res. 2002 Oct;51(10):495-9. doi: 10.1007/pl00012418. [Article]
  7. Duda D, Lorenz W, Celik I: [Mesenteric traction syndrome during the operation of aneurysms of the abdominal aorta--histamine release and prophylaxis with antihistaminics]. Anaesthesiol Reanim. 2003;28(4):97-103. [Article]
  8. Kirch W, Hutt HJ, Heidemann H, Ramsch K, Janisch HD, Ohnhaus EE: Drug interactions with nitrendipine. J Cardiovasc Pharmacol. 1984;6 Suppl 7:S982-5. [Article]
  9. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
  10. DPD Approved Drug Products: Cimetidine (200, 300, 400, 600, 800 mg) [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the biosynthesis of adrenal corticoids (PubMed:12530636, PubMed:1518866, PubMed:1775135, PubMed:18215163, PubMed:23322723). Catalyzes a variety of reactions that are essential for many species, including detoxification, defense, and the formation of endogenous chemicals like steroid hormones. Steroid 11beta, 18- and 19-hydroxylase with preferred regioselectivity at 11beta, then 18, and lastly 19 (By similarity). Catalyzes the hydroxylation of 11-deoxycortisol and 11-deoxycorticosterone (21-hydroxyprogesterone) at 11beta position, yielding cortisol or corticosterone, respectively, but cannot produce aldosterone (PubMed:12530636, PubMed:1518866, PubMed:1775135, PubMed:18215163, PubMed:23322723). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate for hydroxylation and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:18215163). Due to its lack of 18-oxidation activity, it is incapable of generating aldosterone (PubMed:23322723). Could also be involved in the androgen metabolic pathway (Probable)
Specific Function
Corticosterone 18-monooxygenase activity
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
Molecular Weight
57572.44 Da
References
  1. Kenyon CJ, Fraser R, Birnie GG, Connell JM, Lever AF: Dose related in vitro effects of ranitidine and cimetidine on basal and ACTH-stimulated steroidogenesis. Gut. 1986 Oct;27(10):1143-6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Specific Function
Arachidonic acid epoxygenase activity
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function
(r)-limonene 6-monooxygenase activity
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Furuta S, Kamada E, Suzuki T, Sugimoto T, Kawabata Y, Shinozaki Y, Sano H: Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine and omeprazole. Xenobiotica. 2001 Jan;31(1):1-10. doi: 10.1080/00498250110035615. [Article]
  2. Pino MA, Azer SA: Cimetidine . [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
Specific Function
4-nitrophenol 2-monooxygenase activity
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Ohashi K, Sakamoto K, Sudo T, Tateishi T, Fujimura A, Shiga T, Ebihara A: Effects of diltiazem and cimetidine on theophylline oxidative metabolism. J Clin Pharmacol. 1993 Dec;33(12):1233-7. [Article]
  2. Knodell RG, Browne DG, Gwozdz GP, Brian WR, Guengerich FP: Differential inhibition of individual human liver cytochromes P-450 by cimetidine. Gastroenterology. 1991 Dec;101(6):1680-91. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Essential hepatic enzyme that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including drugs as well as dietary compounds (PubMed:10759686, PubMed:30381441, PubMed:32156684). Plays an important role in the metabolism of trimethylamine (TMA), via the production of trimethylamine N-oxide (TMAO) metabolite (PubMed:9776311). TMA is generated by the action of gut microbiota using dietary precursors such as choline, choline containing compounds, betaine or L-carnitine. By regulating TMAO concentration, FMO3 directly impacts both platelet responsiveness and rate of thrombus formation (PubMed:29981269)
Specific Function
Albendazole monooxygenase activity
Gene Name
FMO3
Uniprot ID
P31513
Uniprot Name
Flavin-containing monooxygenase 3
Molecular Weight
60032.975 Da
References
  1. Cashman JR: Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism. Curr Drug Metab. 2000 Sep;1(2):181-91. [Article]
  2. Cashman JR, Park SB, Berkman CE, Cashman LE: Role of hepatic flavin-containing monooxygenase 3 in drug and chemical metabolism in adult humans. Chem Biol Interact. 1995 Apr 28;96(1):33-46. [Article]
  3. Hai X, Adams E, Hoogmartens J, Van Schepdael A: Enantioselective in-line and off-line CE methods for the kinetic study on cimetidine and its chiral metabolites with reference to flavin-containing monooxygenase genetic isoforms. Electrophoresis. 2009 Apr;30(7):1248-57. doi: 10.1002/elps.200800604. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Broad spectrum monooxygenase that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including xenobiotics (PubMed:32156684). Catalyzes the S-oxygenation of hypotaurine to produce taurine, an organic osmolyte involved in cell volume regulation as well as a variety of cytoprotective and developmental processes (PubMed:32156684). In vitro, catalyzes the N-oxygenation of trimethylamine (TMA) to produce trimethylamine N-oxide (TMAO) and could therefore participate to the detoxification of this compound that is generated by the action of gut microbiota from dietary precursors such as choline, choline containing compounds, betaine or L-carnitine (By similarity)
Specific Function
Flavin adenine dinucleotide binding
Gene Name
FMO1
Uniprot ID
Q01740
Uniprot Name
Flavin-containing monooxygenase 1
Molecular Weight
60310.285 Da
References
  1. Hai X, Adams E, Hoogmartens J, Van Schepdael A: Enantioselective in-line and off-line CE methods for the kinetic study on cimetidine and its chiral metabolites with reference to flavin-containing monooxygenase genetic isoforms. Electrophoresis. 2009 Apr;30(7):1248-57. doi: 10.1002/elps.200800604. [Article]
  2. Cashman JR: Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism. Curr Drug Metab. 2000 Sep;1(2):181-91. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function
Aromatase activity
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58406.915 Da
References
  1. Martinez C, Albet C, Agundez JA, Herrero E, Carrillo JA, Marquez M, Benitez J, Ortiz JA: Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999 Apr;65(4):369-76. doi: 10.1016/S0009-9236(99)70129-3. [Article]
  2. Pino MA, Azer SA: Cimetidine . [Article]
  3. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function
Anandamide 11,12 epoxidase activity
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Martinez C, Albet C, Agundez JA, Herrero E, Carrillo JA, Marquez M, Benitez J, Ortiz JA: Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999 Apr;65(4):369-76. doi: 10.1016/S0009-9236(99)70129-3. [Article]
  2. Orishiki M, Matsuo Y, Nishioka M, Ichikawa Y: In vivo administration of H2 blockers, cimetidine and ranitidine, reduced the contents of the cytochrome P450IID (CYP2D) subfamily and their activities in rat liver microsomes. Int J Biochem. 1994 Jun;26(6):751-8. [Article]
  3. Ishii Y, Nakamura K, Tsutsumi K, Kotegawa T, Nakano S, Nakatsuka K: Drug interaction between cimetidine and timolol ophthalmic solution: effect on heart rate and intraocular pressure in healthy Japanese volunteers. J Clin Pharmacol. 2000 Feb;40(2):193-9. [Article]
  4. Furuta S, Kamada E, Suzuki T, Sugimoto T, Kawabata Y, Shinozaki Y, Sano H: Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine and omeprazole. Xenobiotica. 2001 Jan;31(1):1-10. doi: 10.1080/00498250110035615. [Article]
  5. Pino MA, Azer SA: Cimetidine . [Article]
  6. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
Specific Function
(r)-limonene 6-monooxygenase activity
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55944.565 Da
References
  1. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [Article]
  2. Furuta S, Kamada E, Suzuki T, Sugimoto T, Kawabata Y, Shinozaki Y, Sano H: Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine and omeprazole. Xenobiotica. 2001 Jan;31(1):1-10. doi: 10.1080/00498250110035615. [Article]
  3. Satoh T, Fujita KI, Munakata H, Itoh S, Nakamura K, Kamataki T, Itoh S, Yoshizawa I: Studies on the interactions between drugs and estrogen: analytical method for prediction system of gynecomastia induced by drugs on the inhibitory metabolism of estradiol using Escherichia coli coexpressing human CYP3A4 with human NADPH-cytochrome P450 reductase. Anal Biochem. 2000 Nov 15;286(2):179-86. doi: 10.1006/abio.1999.4775. [Article]
  4. Park EJ, Cho HY, Lee YB: Effect of Cimetidine and Phenobarbital on metabolite kinetics of Omeprazole in rats. Arch Pharm Res. 2005 Oct;28(10):1196-202. [Article]
  5. Flockhart Table of Drug Interactions [Link]
Details
10. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y: Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther. 2002 Aug;302(2):510-5. [Article]
  2. Satoh T, Fujita KI, Munakata H, Itoh S, Nakamura K, Kamataki T, Itoh S, Yoshizawa I: Studies on the interactions between drugs and estrogen: analytical method for prediction system of gynecomastia induced by drugs on the inhibitory metabolism of estradiol using Escherichia coli coexpressing human CYP3A4 with human NADPH-cytochrome P450 reductase. Anal Biochem. 2000 Nov 15;286(2):179-86. doi: 10.1006/abio.1999.4775. [Article]
  3. Park EJ, Cho HY, Lee YB: Effect of Cimetidine and Phenobarbital on metabolite kinetics of Omeprazole in rats. Arch Pharm Res. 2005 Oct;28(10):1196-202. [Article]
  4. Martinez C, Albet C, Agundez JA, Herrero E, Carrillo JA, Marquez M, Benitez J, Ortiz JA: Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999 Apr;65(4):369-76. doi: 10.1016/S0009-9236(99)70129-3. [Article]
  5. Flockhart Table of Drug Interactions [Link]
  6. Drug Interactions & Labeling - FDA [Link]
  7. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
Specific Function
Aromatase activity
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Martinez C, Albet C, Agundez JA, Herrero E, Carrillo JA, Marquez M, Benitez J, Ortiz JA: Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999 Apr;65(4):369-76. doi: 10.1016/S0009-9236(99)70129-3. [Article]
  2. Flockhart Table of Drug Interactions [Link]
  3. Drug Interactions & Labeling - FDA [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
Antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
References
  1. Wilson CJ, Bogoyevitch MA, Winzor DJ: Interaction of cimetidine with human serum albumin. Biochem Pharmacol. 1990 Oct 1;40(7):1672-3. doi: 10.1016/0006-2952(90)90472-w. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function
Abc-type xenobiotic transporter activity
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
ATP-dependent translocase ABCB1
Molecular Weight
141477.255 Da
References
  1. Romiti N, Tramonti G, Chieli E: Influence of different chemicals on MDR-1 P-glycoprotein expression and activity in the HK-2 proximal tubular cell line. Toxicol Appl Pharmacol. 2002 Sep 1;183(2):83-91. [Article]
  2. Lentz KA, Polli JW, Wring SA, Humphreys JE, Polli JE: Influence of passive permeability on apparent P-glycoprotein kinetics. Pharm Res. 2000 Dec;17(12):1456-60. [Article]
  3. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [Article]
  4. van der Sandt IC, Blom-Roosemalen MC, de Boer AG, Breimer DD: Specificity of doxorubicin versus rhodamine-123 in assessing P-glycoprotein functionality in the LLC-PK1, LLC-PK1:MDR1 and Caco-2 cell lines. Eur J Pharm Sci. 2000 Sep;11(3):207-14. [Article]
  5. Ito T, Yano I, Tanaka K, Inui KI: Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1. J Pharmacol Exp Ther. 1997 Aug;282(2):955-60. [Article]
  6. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [Article]
  7. Taur JS, Rodriguez-Proteau R: Effects of dietary flavonoids on the transport of cimetidine via P-glycoprotein and cationic transporters in Caco-2 and LLC-PK1 cell models. Xenobiotica. 2008 Dec;38(12):1536-50. doi: 10.1080/00498250802499467. [Article]
  8. Choi YH, Yu AM: ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development. Curr Pharm Des. 2014;20(5):793-807. doi: 10.2174/138161282005140214165212. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
Acetylcholine transmembrane transporter activity
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. [Article]
  2. Motohashi H, Uwai Y, Hiramoto K, Okuda M, Inui K: Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Eur J Pharmacol. 2004 Oct 25;503(1-3):25-30. [Article]
  3. Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002 Aug 23;296(3):644-50. [Article]
  4. Urakami Y, Okuda M, Masuda S, Saito H, Inui KI: Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J Pharmacol Exp Ther. 1998 Nov;287(2):800-5. [Article]
  5. Okuda M, Urakami Y, Saito H, Inui K: Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochim Biophys Acta. 1999 Mar 4;1417(2):224-31. [Article]
  6. Pan BF, Sweet DH, Pritchard JB, Chen R, Nelson JA: A transfected cell model for the renal toxin transporter, rOCT2. Toxicol Sci. 1999 Feb;47(2):181-6. [Article]
  7. Dudley AJ, Bleasby K, Brown CD: The organic cation transporter OCT2 mediates the uptake of beta-adrenoceptor antagonists across the apical membrane of renal LLC-PK(1) cell monolayers. Br J Pharmacol. 2000 Sep;131(1):71-9. [Article]
  8. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
  9. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
Specific Function
(r)-carnitine transmembrane transporter activity
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002 Aug 23;296(3):644-50. [Article]
  2. Zhang L, Dresser MJ, Chun JK, Babbitt PC, Giacomini KM: Cloning and functional characterization of a rat renal organic cation transporter isoform (rOCT1A). J Biol Chem. 1997 Jun 27;272(26):16548-54. [Article]
  3. Urakami Y, Okuda M, Masuda S, Saito H, Inui KI: Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J Pharmacol Exp Ther. 1998 Nov;287(2):800-5. [Article]
  4. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [Article]
  5. Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y: Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther. 2002 Aug;302(2):510-5. [Article]
  6. Lee WK, Reichold M, Edemir B, Ciarimboli G, Warth R, Koepsell H, Thevenod F: Organic cation transporters OCT1, 2, and 3 mediate high-affinity transport of the mutagenic vital dye ethidium in the kidney proximal tubule. Am J Physiol Renal Physiol. 2009 Jun;296(6):F1504-13. doi: 10.1152/ajprenal.90754.2008. Epub 2009 Apr 8. [Article]
  7. Song IS, Kong TY, Jeong HU, Kim EN, Kwon SS, Kang HE, Choi SZ, Son M, Lee HS: Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo. BMC Complement Altern Med. 2014 Jul 17;14:251. doi: 10.1186/1472-6882-14-251. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924). Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter (PubMed:12538837). Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754). May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity). Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837). Also transports guanidine (PubMed:10966924). May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity)
Specific Function
Monoamine transmembrane transporter activity
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Grundemann D, Schechinger B, Rappold GA, Schomig E: Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci. 1998 Sep;1(5):349-51. [Article]
  2. Wu X, Huang W, Ganapathy ME, Wang H, Kekuda R, Conway SJ, Leibach FH, Ganapathy V: Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58. [Article]
  3. Kekuda R, Prasad PD, Wu X, Wang H, Fei YJ, Leibach FH, Ganapathy V: Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J Biol Chem. 1998 Jun 26;273(26):15971-9. [Article]
  4. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [Article]
  5. Chen L, Pawlikowski B, Schlessinger A, More SS, Stryke D, Johns SJ, Portman MA, Chen E, Ferrin TE, Sali A, Giacomini KM: Role of organic cation transporter 3 (SLC22A3) and its missense variants in the pharmacologic action of metformin. Pharmacogenet Genomics. 2010 Nov;20(11):687-99. doi: 10.1097/FPC.0b013e32833fe789. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine (PubMed:10454528, PubMed:10525100, PubMed:10966938, PubMed:17509700, PubMed:20722056, PubMed:33124720). Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528, PubMed:10525100, PubMed:10966938). In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from Bacillus Subtilis wich induces cytoprotective heat shock proteins contributing to intestinal homeostasis (PubMed:18005709). May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
(r)-carnitine transmembrane transporter activity
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Organic cation/carnitine transporter 2
Molecular Weight
62751.08 Da
References
  1. Wu X, Prasad PD, Leibach FH, Ganapathy V: cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589-95. [Article]
  2. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [Article]
  3. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
Specific Function
Alpha-ketoglutarate transmembrane transporter activity
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. [Article]
  2. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. [Article]
  3. Nagata Y, Kusuhara H, Endou H, Sugiyama Y: Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus. Mol Pharmacol. 2002 May;61(5):982-8. [Article]
  4. Burckhardt BC, Brai S, Wallis S, Krick W, Wolff NA, Burckhardt G: Transport of cimetidine by flounder and human renal organic anion transporter 1. Am J Physiol Renal Physiol. 2003 Mar;284(3):F503-9. Epub 2002 Nov 12. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
Specific Function
Organic anion transmembrane transporter activity
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Organic anion transporter 3
Molecular Weight
59855.585 Da
References
  1. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. [Article]
  2. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. [Article]
  3. Motohashi H, Uwai Y, Hiramoto K, Okuda M, Inui K: Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Eur J Pharmacol. 2004 Oct 25;503(1-3):25-30. [Article]
  4. Ohtsuki S, Kikkawa T, Mori S, Hori S, Takanaga H, Otagiri M, Terasaki T: Mouse reduced in osteosclerosis transporter functions as an organic anion transporter 3 and is localized at abluminal membrane of blood-brain barrier. J Pharmacol Exp Ther. 2004 Jun;309(3):1273-81. Epub 2004 Feb 4. [Article]
  5. Kobayashi Y, Ohshiro N, Tsuchiya A, Kohyama N, Ohbayashi M, Yamamoto T: Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83. [Article]
  6. Nagata Y, Kusuhara H, Endou H, Sugiyama Y: Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus. Mol Pharmacol. 2002 May;61(5):982-8. [Article]
  7. Mori S, Takanaga H, Ohtsuki S, Deguchi T, Kang YS, Hosoya K, Terasaki T: Rat organic anion transporter 3 (rOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells. J Cereb Blood Flow Metab. 2003 Apr;23(4):432-40. [Article]
  8. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [Article]
  9. Bakhiya A, Bahn A, Burckhardt G, Wolff N: Human organic anion transporter 3 (hOAT3) can operate as an exchanger and mediate secretory urate flux. Cell Physiol Biochem. 2003;13(5):249-56. [Article]
  10. Tahara H, Kusuhara H, Chida M, Fuse E, Sugiyama Y: Is the monkey an appropriate animal model to examine drug-drug interactions involving renal clearance? Effect of probenecid on the renal elimination of H2 receptor antagonists. J Pharmacol Exp Ther. 2006 Mar;316(3):1187-94. Epub 2005 Nov 16. [Article]
  11. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16330770, PubMed:17509534). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
Antiporter activity
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Lai Y, Sampson KE, Balogh LM, Brayman TG, Cox SR, Adams WJ, Kumar V, Stevens JC: Preclinical and clinical evidence for the collaborative transport and renal secretion of an oxazolidinone antibiotic by organic anion transporter 3 (OAT3/SLC22A8) and multidrug and toxin extrusion protein 1 (MATE1/SLC47A1). J Pharmacol Exp Ther. 2010 Sep 1;334(3):936-44. doi: 10.1124/jpet.110.170753. Epub 2010 Jun 2. [Article]
  2. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [Article]
  3. Burt HJ, Neuhoff S, Almond L, Gaohua L, Harwood MD, Jamei M, Rostami-Hodjegan A, Tucker GT, Rowland-Yeo K: Metformin and cimetidine: Physiologically based pharmacokinetic modelling to investigate transporter mediated drug-drug interactions. Eur J Pharm Sci. 2016 Jun 10;88:70-82. doi: 10.1016/j.ejps.2016.03.020. Epub 2016 Mar 25. [Article]
  4. Elsby R, Chidlaw S, Outteridge S, Pickering S, Radcliffe A, Sullivan R, Jones H, Butler P: Mechanistic in vitro studies confirm that inhibition of the renal apical efflux transporter multidrug and toxin extrusion (MATE) 1, and not altered absorption, underlies the increased metformin exposure observed in clinical interactions with cimetidine, trimethoprim or pyrimethamine. Pharmacol Res Perspect. 2017 Oct;5(5). doi: 10.1002/prp2.357. [Article]
  5. FDA interactions table [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations (PubMed:10215651, PubMed:15107849, PubMed:15795384, PubMed:16729965, PubMed:20601551, PubMed:22206629, PubMed:22569296, PubMed:29530864). Functions as a Na(+)-dependent and pH-dependent high affinity microbial symporter of potent food-derived antioxidant ergothioeine (PubMed:15795384, PubMed:29530864, PubMed:33124720). Transports one sodium ion with one ergothioeine molecule (By similarity). Involved in the absorption of ergothioneine from the luminal/apical side of the small intestine and renal tubular cells, and into non-parenchymal liver cells, thereby contributing to maintain steady-state ergothioneine level in the body (PubMed:20601551). Also mediates the bidirectional transport of acetycholine, although the exact transport mechanism has not been fully identified yet (PubMed:22206629). Most likely exports anti-inflammatory acetylcholine in non-neuronal tissues, thereby contributing to the non-neuronal cholinergic system (PubMed:22206629, PubMed:22569296). Displays a general physiological role linked to better survival by controlling inflammation and oxidative stress, which may be related to ergothioneine and acetycholine transports (PubMed:15795384, PubMed:22206629). May also function as a low-affinity Na(+)-dependent transporter of L-carnitine through the mitochondrial membrane, thereby maintaining intracellular carnitine homeostasis (PubMed:10215651, PubMed:15107849, PubMed:16729965). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (PubMed:35307651)
Specific Function
Acetylcholine transmembrane transporter activity
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. [Article]
  2. Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, Ganapathy V: Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta. 2000 Jun 1;1466(1-2):315-27. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds (PubMed:10660625, PubMed:11907186, PubMed:15037815, PubMed:15102942, PubMed:15291761, PubMed:15576633, PubMed:17229912, PubMed:18501590, PubMed:26277985, PubMed:28027879). May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus (PubMed:12409283). Maybe also be involved in placental urate homeostasis (PubMed:17229912). Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates (PubMed:15037815, PubMed:17229912). Organic anion glutarate acts as conteranion for E1S renal uptake (PubMed:15037815, PubMed:17229912). Possible transport mode may also include DHEA-S/E1S exchange (PubMed:28027879). Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) (PubMed:17229912). Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion (PubMed:11907186). Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A (PubMed:10660625, PubMed:26277985). Mediates the unidirectional efflux of glutamate and aspartate (PubMed:28027879). Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S (PubMed:26277985)
Specific Function
Organic anion transmembrane transporter activity
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
References
  1. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Functions as a Na(+)-independent bidirectional multispecific transporter (PubMed:11327718, PubMed:18216183, PubMed:21446918, PubMed:28945155). Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively (PubMed:11327718, PubMed:25904762). Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2'deoxyguanosine and GMP being the preferred substrates (PubMed:11327718, PubMed:18216183, PubMed:26377792, PubMed:28945155). Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways (PubMed:18216183, PubMed:26377792). Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood (PubMed:21446918). Involved in renal secretion and possible reabsorption of creatinine (PubMed:25904762, PubMed:28945155). Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion (Probable). Also transports alpha-ketoglutarate and urate (PubMed:11327718, PubMed:26377792). Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified (PubMed:26377792)
Specific Function
Alpha-ketoglutarate transmembrane transporter activity
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
Molecular Weight
60025.025 Da
References
  1. Kobayashi Y, Ohshiro N, Shibusawa A, Sasaki T, Tokuyama S, Sekine T, Endou H, Yamamoto T: Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol. 2002 Jul;62(1):7-14. [Article]
  2. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
Specific Function
Abc-type bile acid transporter activity
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Zhang J, He K, Cai L, Chen YC, Yang Y, Shi Q, Woolf TF, Ge W, Guo L, Borlak J, Tong W: Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse. Chem Biol Interact. 2016 Aug 5;255:45-54. doi: 10.1016/j.cbi.2016.03.019. Epub 2016 Mar 19. [Article]
  2. Wilson A. (2016). New horizons in predictive drug metabolism and pharmacokinetics. The Royal Society of Chemistry. [ISBN:978-1-84973-828-6]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Data based on in vitro studies.
General Function
Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
Specific Function
Antiporter activity
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [Article]
  2. Ito S, Kusuhara H, Yokochi M, Toyoshima J, Inoue K, Yuasa H, Sugiyama Y: Competitive inhibition of the luminal efflux by multidrug and toxin extrusions, but not basolateral uptake by organic cation transporter 2, is the likely mechanism underlying the pharmacokinetic drug-drug interactions caused by cimetidine in the kidney. J Pharmacol Exp Ther. 2012 Feb;340(2):393-403. doi: 10.1124/jpet.111.184986. Epub 2011 Nov 9. [Article]
  3. Dumitras S, Sechaud R, Drollmann A, Pal P, Vaidyanathan S, Camenisch G, Kaiser G: Effect of cimetidine, a model drug for inhibition of the organic cation transport (OCT2/MATE1) in the kidney, on the pharmacokinetics of glycopyrronium. Int J Clin Pharmacol Ther. 2013 Oct;51(10):771-9. doi: 10.5414/CP201946. [Article]
  4. Yonezawa A, Inui K: Importance of the multidrug and toxin extrusion MATE/SLC47A family to pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics. Br J Pharmacol. 2011 Dec;164(7):1817-25. doi: 10.1111/j.1476-5381.2011.01394.x. [Article]
  5. FDA interactions table [Link]

Drug created at June 13, 2005 13:24 / Updated at September 16, 2024 01:05