Explore a selection of our essential drug information below, or:
Identification
- Summary
Desflurane is a general inhalation anesthetic for inpatient and outpatient surgery in adults.
- Brand Names
- Suprane
- Generic Name
- Desflurane
- DrugBank Accession Number
- DB01189
- Background
Desflurane, or I-653, a a volatile anesthetic that is more rapidly cleared and less metabolized than previous inhaled anesthetics such as methoxyflurane, sevoflurane, enflurane, or isoflurane.4,2,21. It was developed in the late 1980s out of a need for a more rapidly acting and rapidly cleared inhaled anesthetic.19,20
Desflurane was granted FDA approval on 18 September 1992.22
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Desflurane (DB01189)
- Weight
- Average: 168.0378
Monoisotopic: 168.000983916 - Chemical Formula
- C3H2F6O
- Synonyms
- (±)-2-difluoromethyl 1,2,2,2-tetrafluoroethyl ether
- 1,1,1,2-tetrafluoro-2-(difluoromethoxy)ethane
- Desflurane
- Desflurano
- Desfluranum
- Difluoromethyl 1,2,2,2-tetrafluoroethyl ether
Pharmacology
- Indication
Desflurane is indicated for the induction and maintenance of anesthesia in adults, as well as the maintenance of anesthesia in pediatric patients.22
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Therapies
- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Desflurane is a general inhalation anesthetic.22 It has a short duration of action as it is rapidly cleared.22 Patients should be counselled regarding the risks of malignant hyperthermia, perioperative hyperkalemia, respiratory adverse reactions in pediatric patients, QTc prolongation, hepatobiliary disorders, pediatric neurotoxicity, and postoperative agitation in children.22
- Mechanism of action
The mechanism of inhalational anesthetics is still not fully understood.5 They can block excitatory ion channels and increase the activity of inhibitory ion channels.5 The most notable agonism is at the GABAA channel.9 Desflurane is also an agonist of glycine receptors,10 antagonist of glutamate receptors,11 inducer of potassium voltage gated channels,12 and inhibits both NADH-ubiquinone oxioreductase chain 113 and calcium transporting ATPases.14
An older school of thought is the unitary theory of general anesthetic action, suggesting that desflurane affects the lipid bilayer of cells.5,7 Studies of other halogenated inhalational anesthetics have shown that the lipid bilayer spreads out more thinly as the anesthetic incorporates into the bilayer.6 However, the anesthetic does not bind to lipid heads or acyl chains of hydrocarbons in the bilayer.6 The effect of incorporating into the lipid bilayer is not well described.6,22 By incorporating into the lipid bilayer, anesthetics may introduce disorder in the lipids, leading to some indirect effect on ion channels.7 However, this theory remains controversial.8
Target Actions Organism AGABA(A) Receptor positive allosteric modulatorHumans AGlycine receptor subunit alpha-1 agonistHumans AGlutamate receptor 1 antagonistHumans APotassium voltage-gated channel subfamily A member 1 inducerHumans ANADH-ubiquinone oxidoreductase chain 1 inhibitorHumans ACalcium transporting ATPases inhibitorHumans UATP synthase subunit delta, mitochondrial other/unknownHumans - Absorption
Data regarding the Cmax, Tmax, and AUC of desflurane are not readily available.22
- Volume of distribution
Desflurane has a median volume of distribution of 612 mL/kg.18
- Protein binding
Desflurane is bound to human serum albumin in plasma.17
- Metabolism
Desflurane is minimally defluorinated by CYP2E1,2 to the extent that serum fluoride levels do not increase above baseline levels.4
Hover over products below to view reaction partners
- Route of elimination
Initially, desflurane is rapidly eliminated from the lungs.16 A small amount of the metabolite trifluoroacetic acid is eliminated in the urine3 and only 0.02% of an inhaled dose is recovered as urinary metabolites.22
- Half-life
Desflurane has a terminal elimination half life of 8.16 ± 3.15 minutes.15
- Clearance
A 26 g dose of desflurane is 90% eliminated from the brain after 33 hours.1 The metabolite trifluoroacetic acid has a urinary clearance rate of 0.169 ± 0.107 µmol/L.4
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Patients experiencing a desflurane overdose may experience deepening anesthesia, cardiac or respiratory depression.22 In the event of an overdose, patients may require symptomatic and supportive treatment to maintain airway, breathing, and circulation.22 Discontinue desflurane.22
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Voltage-dependent L-type calcium channel subunit alpha-1S --- Not Available c.3257G>A / c.520C>T ADR Inferred Malignant hyperthermia. Details Ryanodine receptor 1 --- Not Available c.103T>C / c.487C>T … show all ADR Inferred Malignant hyperthermia. Details
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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Desflurane is combined with 1,2-Benzodiazepine. Abaloparatide The risk or severity of adverse effects can be increased when Desflurane is combined with Abaloparatide. Acebutolol Desflurane may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of hypertension can be increased when Desflurane is combined with Aceclofenac. Acemetacin The risk or severity of hypertension can be increased when Desflurane is combined with Acemetacin. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Desflurane Liquid 100 % v/v Respiratory (inhalation) Blue Zone Technologies Ltd Not applicable Not applicable Canada 
Desflurane Liquid 250 mL/250mL Respiratory (inhalation) Piramal Critical Care Inc 2023-02-14 Not applicable US 
Suprane Liquid 240 mL/240mL Respiratory (inhalation) Baxter Healthcare Corporation 1992-09-18 Not applicable US Suprane Liquid 1.5 g/1mL Respiratory (inhalation) Baxter Healthcare Corporation 2006-08-14 2006-08-14 US Suprane Liquid 100 % v/v Respiratory (inhalation) Baxter Laboratories 1996-12-23 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Desflurane Liquid 240 mL/240mL Respiratory (inhalation) Sandoz Inc. 2018-02-26 Not applicable US
Categories
- ATC Codes
- N01AB07 — Desflurane
- Drug Categories
- Agents that produce hypertension
- Anesthetics
- Anesthetics, General
- Anesthetics, Inhalation
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 Substrates
- Ethers
- Ethyl Ethers
- Hydrocarbons, Fluorinated
- Hydrocarbons, Halogenated
- Hypotensive Agents
- Methyl Ethers
- Nervous System
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as organofluorides. These are compounds containing a chemical bond between a carbon atom and a fluorine atom.
- Kingdom
- Organic compounds
- Super Class
- Organohalogen compounds
- Class
- Organofluorides
- Sub Class
- Not Available
- Direct Parent
- Organofluorides
- Alternative Parents
- Organooxygen compounds / Hydrocarbon derivatives / Alkyl fluorides
- Substituents
- Aliphatic acyclic compound / Alkyl fluoride / Alkyl halide / Hydrocarbon derivative / Organic oxygen compound / Organofluoride / Organooxygen compound
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- organofluorine compound (CHEBI:4445)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- CRS35BZ94Q
- CAS number
- 57041-67-5
- InChI Key
- DPYMFVXJLLWWEU-UHFFFAOYSA-N
- InChI
- InChI=1S/C3H2F6O/c4-1(3(7,8)9)10-2(5)6/h1-2H
- IUPAC Name
- 2-(difluoromethoxy)-1,1,1,2-tetrafluoroethane
- SMILES
- FC(F)OC(F)C(F)(F)F
References
- Synthesis Reference
Leonid A. Rozov, Chialang Huang, Gerald G. Vernice, "Synthesis of desflurane." U.S. Patent US5205914, issued June, 1991.
US5205914- General References
- Lockwood G: Theoretical context-sensitive elimination times for inhalation anaesthetics. Br J Anaesth. 2010 May;104(5):648-55. doi: 10.1093/bja/aeq051. Epub 2010 Mar 16. [Article]
- Kharasch ED, Thummel KE: Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, and methoxyflurane. Anesthesiology. 1993 Oct;79(4):795-807. [Article]
- Koblin DD: Characteristics and implications of desflurane metabolism and toxicity. Anesth Analg. 1992 Oct;75(4 Suppl):S10-6. [Article]
- Sutton TS, Koblin DD, Gruenke LD, Weiskopf RB, Rampil IJ, Waskell L, Eger EI 2nd: Fluoride metabolites after prolonged exposure of volunteers and patients to desflurane. Anesth Analg. 1991 Aug;73(2):180-5. doi: 10.1213/00000539-199108000-00011. [Article]
- Khan J, Liu M: Desflurane . [Article]
- Tu K, Tarek M, Klein ML, Scharf D: Effects of anesthetics on the structure of a phospholipid bilayer: molecular dynamics investigation of halothane in the hydrated liquid crystal phase of dipalmitoylphosphatidylcholine. Biophys J. 1998 Nov;75(5):2123-34. doi: 10.1016/S0006-3495(98)77655-6. [Article]
- Krasowski MD: Contradicting a unitary theory of general anesthetic action: a history of three compounds from 1901 to 2001. Bull Anesth Hist. 2003 Jul;21(3):1, 4-8, 21 passim. doi: 10.1016/s1522-8649(03)50031-2. [Article]
- Herold KF, Sanford RL, Lee W, Andersen OS, Hemmings HC Jr: Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3109-3114. doi: 10.1073/pnas.1611717114. Epub 2017 Mar 6. [Article]
- Ton HT, Phan TX, Abramyan AM, Shi L, Ahern GP: Identification of a putative binding site critical for general anesthetic activation of TRPA1. Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):3762-3767. doi: 10.1073/pnas.1618144114. Epub 2017 Mar 20. [Article]
- Grasshoff C, Antkowiak B: Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats. Br J Anaesth. 2006 Nov;97(5):687-94. doi: 10.1093/bja/ael239. Epub 2006 Sep 13. [Article]
- Dildy-Mayfield JE, Eger EI 2nd, Harris RA: Anesthetics produce subunit-selective actions on glutamate receptors. J Pharmacol Exp Ther. 1996 Mar;276(3):1058-65. [Article]
- Matchett GA, Allard MW, Martin RD, Zhang JH: Neuroprotective effect of volatile anesthetic agents: molecular mechanisms. Neurol Res. 2009 Mar;31(2):128-34. doi: 10.1179/174313209X393546. [Article]
- Hanley PJ, Ray J, Brandt U, Daut J: Halothane, isoflurane and sevoflurane inhibit NADH:ubiquinone oxidoreductase (complex I) of cardiac mitochondria. J Physiol. 2002 Nov 1;544(Pt 3):687-93. [Article]
- Kosk-Kosicka D: Plasma membrane Ca(2+)-ATPase as a target for volatile anesthetics. Adv Pharmacol. 1994;31:313-22. [Article]
- Behne M, Wilke HJ, Lischke V: Recovery and pharmacokinetic parameters of desflurane, sevoflurane, and isoflurane in patients undergoing urologic procedures. J Clin Anesth. 1999 Sep;11(6):460-5. doi: 10.1016/s0952-8180(99)00082-3. [Article]
- Lu CC, Tsai CS, Hu OY, Chen RM, Chen TL, Ho ST, Gan TJ: Pharmacokinetics of desflurane elimination from respiratory gas and blood during the 20 minutes after cardiac surgery. J Formos Med Assoc. 2013 Apr;112(4):185-92. doi: 10.1016/j.jfma.2012.01.017. Epub 2012 May 20. [Article]
- Sawas AH, Pentyala SN, Rebecchi MJ: Binding of volatile anesthetics to serum albumin: measurements of enthalpy and solvent contributions. Biochemistry. 2004 Oct 5;43(39):12675-85. [Article]
- Wissing H, Kuhn I, Rietbrock S, Fuhr U: Pharmacokinetics of inhaled anaesthetics in a clinical setting: comparison of desflurane, isoflurane and sevoflurane. Br J Anaesth. 2000 Apr;84(4):443-9. doi: 10.1093/oxfordjournals.bja.a013467. [Article]
- Eger EI 2nd: Partition coefficients of I-653 in human blood, saline, and olive oil. Anesth Analg. 1987 Oct;66(10):971-3. [Article]
- Eger EI 2nd, Johnson BH: Rates of awakening from anesthesia with I-653, halothane, isoflurane, and sevoflurane: a test of the effect of anesthetic concentration and duration in rats. Anesth Analg. 1987 Oct;66(10):977-82. [Article]
- Eger EI 3rd: Stability of I-653 in soda lime. Anesth Analg. 1987 Oct;66(10):983-5. [Article]
- FDA Approved Drug Products: Suprane (Desflurane) Inhalational Liquid [Link]
- External Links
- Human Metabolome Database
- HMDB0015320
- KEGG Drug
- D00546
- KEGG Compound
- C07519
- PubChem Compound
- 42113
- PubChem Substance
- 46505270
- ChemSpider
- 38403
- 27340
- ChEBI
- 4445
- ChEMBL
- CHEMBL1200733
- Therapeutic Targets Database
- DAP000693
- PharmGKB
- PA164749136
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Desflurane
- FDA label
- Download (174 KB)
- MSDS
- Download (51.1 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 Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Other Lung Cancer 1 somestatus stop reason just information to hide Not Available Completed Not Available Aging / Healthy Volunteers (HV) 1 somestatus stop reason just information to hide Not Available Completed Not Available Anesthesia therapy / Surgery 1 somestatus stop reason just information to hide Not Available Completed Not Available Anesthetics, Inhalation 1 somestatus stop reason just information to hide Not Available Completed Not Available Cohort Study 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Baxter International Inc.
- General Injectables and Vaccines Inc.
- Dosage Forms
Form Route Strength Solution Respiratory (inhalation) 100 % Liquid Respiratory (inhalation) 250 mL/250mL Inhalant Respiratory (inhalation) Inhalant Respiratory (inhalation) 100 % Solution Respiratory (inhalation) Aerosol Respiratory (inhalation) 240 ML Aerosol Respiratory (inhalation) 100 ml/100ml Inhalant Respiratory (inhalation) 240 mL/240mL Liquid Respiratory (inhalation) 1.5 g/1mL Liquid Respiratory (inhalation) 100 % v/v Liquid Respiratory (inhalation) 240 mL/240mL Solution Respiratory (inhalation) 100.000 mL Liquid Respiratory (inhalation) 100 % Liquid Respiratory (inhalation) Solution Nasal 100 % Solution Respiratory (inhalation) 100 mL - Prices
Unit description Cost Unit Suprane inhalation liquid 0.76USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5617906 No 1997-04-08 2014-10-08 US
Properties
- State
- Liquid
- Experimental Properties
Property Value Source boiling point (°C) 22.8 °C https://imgcdn.mckesson.com/CumulusWeb/Click_and_learn/SDS_9BAXAC_SUPRANE_INH_LIQ_240ML_6CT.pdf water solubility Negligible Not Available - Predicted Properties
Property Value Source Water Solubility 3.54 mg/mL ALOGPS logP 2.19 ALOGPS logP 2.4 Chemaxon logS -1.7 ALOGPS pKa (Strongest Acidic) 18.87 Chemaxon pKa (Strongest Basic) -4.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 9.23 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 18.12 m3·mol-1 Chemaxon Polarizability 7.89 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9974 Blood Brain Barrier + 0.9941 Caco-2 permeable + 0.626 P-glycoprotein substrate Non-substrate 0.883 P-glycoprotein inhibitor I Non-inhibitor 0.9415 P-glycoprotein inhibitor II Non-inhibitor 0.9027 Renal organic cation transporter Non-inhibitor 0.9311 CYP450 2C9 substrate Non-substrate 0.8676 CYP450 2D6 substrate Non-substrate 0.919 CYP450 3A4 substrate Non-substrate 0.7556 CYP450 1A2 substrate Non-inhibitor 0.6194 CYP450 2C9 inhibitor Non-inhibitor 0.836 CYP450 2D6 inhibitor Non-inhibitor 0.9466 CYP450 2C19 inhibitor Non-inhibitor 0.707 CYP450 3A4 inhibitor Non-inhibitor 0.9604 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8921 Ames test Non AMES toxic 0.9042 Carcinogenicity Carcinogens 0.7045 Biodegradation Not ready biodegradable 0.9566 Rat acute toxicity 1.2690 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9724 hERG inhibition (predictor II) Non-inhibitor 0.909
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0udi-9400000000-9bfc58e3ef0acdde70c6 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0900000000-f05324a0ba17c1fd3d70 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0900000000-6f09baa237443998c9e9 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-2900000000-f13323970286c0fd70d2 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-1900000000-92394e36b4013c2a5d68 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-6900000000-3ad613bc2ff08c4efb2c Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-3900000000-9a6dbc67d2d254d53d7e Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 103.8089234 predictedDarkChem Lite v0.1.0 [M-H]- 131.45085 predictedDeepCCS 1.0 (2019) [M+H]+ 104.7489234 predictedDarkChem Lite v0.1.0 [M+H]+ 133.72801 predictedDeepCCS 1.0 (2019) [M+Na]+ 104.3717234 predictedDarkChem Lite v0.1.0 [M+Na]+ 142.33743 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Positive allosteric modulator
- General Function
- Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:23909897, PubMed:25489750, PubMed:29950725, PubMed:30602789). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:29950725, PubMed:30602789). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:23909897, PubMed:29950725, PubMed:30602789). Alpha-1/GABRA1-containing GABAARs are largely synaptic (By similarity). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:23909897, PubMed:25489750). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response (By similarity). GABAARs containing alpha, beta and epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Alpha-1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (By similarity). Together with rho subunits, may also control neuronal and glial GABAergic transmission in the cerebellum (By similarity)
- Specific Function
- Gaba-a receptor activity
Components:
References
- Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [Article]
- Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Glycine receptors are ligand-gated chloride channels (PubMed:23994010, PubMed:25730860). Channel opening is triggered by extracellular glycine (PubMed:14551753, PubMed:16144831, PubMed:2155780, PubMed:22715885, PubMed:22973015, PubMed:25973519, PubMed:7920629, PubMed:9009272). Channel opening is also triggered by taurine and beta-alanine (PubMed:16144831, PubMed:9009272). Channel characteristics depend on the subunit composition; heteropentameric channels are activated by lower glycine levels and display faster desensitization (PubMed:14551753). Plays an important role in the down-regulation of neuronal excitability (PubMed:8298642, PubMed:9009272). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Channel activity is potentiated by ethanol (PubMed:25973519). Potentiation of channel activity by intoxicating levels of ethanol contribute to the sedative effects of ethanol (By similarity)
- Specific Function
- Extracellularly glycine-gated chloride channel activity
- Gene Name
- GLRA1
- Uniprot ID
- P23415
- Uniprot Name
- Glycine receptor subunit alpha-1
- Molecular Weight
- 52623.35 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Grasshoff C, Antkowiak B: Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats. Br J Anaesth. 2006 Nov;97(5):687-94. doi: 10.1093/bja/ael239. Epub 2006 Sep 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (PubMed:1311100, PubMed:20805473, PubMed:21172611, PubMed:28628100, PubMed:35675825). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (By similarity). In the presence of CACNG2 or CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (PubMed:21172611). Resensitization is blocked by CNIH2 through interaction with CACNG8 in the CACNG8-containing AMPA receptors complex (PubMed:21172611). Calcium (Ca(2+)) permeability depends on subunits composition and, heteromeric channels containing edited GRIA2 subunit are calcium-impermeable. Also permeable to other divalents cations such as strontium(2+) and magnesium(2+) and monovalent cations such as potassium(1+) and lithium(1+) (By similarity)
- Specific Function
- Adenylate cyclase binding
- Gene Name
- GRIA1
- Uniprot ID
- P42261
- Uniprot Name
- Glutamate receptor 1
- Molecular Weight
- 101505.245 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Dildy-Mayfield JE, Eger EI 2nd, Harris RA: Anesthetics produce subunit-selective actions on glutamate receptors. J Pharmacol Exp Ther. 1996 Mar;276(3):1058-65. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:19903818, PubMed:8845167). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12077175, PubMed:17156368). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed:12077175, PubMed:17156368). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19307729, PubMed:19903818, PubMed:19912772, PubMed:19968958). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses (PubMed:11026449, PubMed:17136396). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (PubMed:19307729, PubMed:23903368)
- Specific Function
- Delayed rectifier potassium channel activity
- Gene Name
- KCNA1
- Uniprot ID
- Q09470
- Uniprot Name
- Potassium voltage-gated channel subfamily A member 1
- Molecular Weight
- 56465.01 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Matchett GA, Allard MW, Martin RD, Zhang JH: Neuroprotective effect of volatile anesthetic agents: molecular mechanisms. Neurol Res. 2009 Mar;31(2):128-34. doi: 10.1179/174313209X393546. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- This action is based on the activity of other volatile anesthetics on this target. It is a potential target for desflurane.
- General Function
- Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:1959619). Essential for the catalytic activity and assembly of complex I (PubMed:1959619, PubMed:26929434)
- Specific Function
- Nadh dehydrogenase (ubiquinone) activity
- Gene Name
- MT-ND1
- Uniprot ID
- P03886
- Uniprot Name
- NADH-ubiquinone oxidoreductase chain 1
- Molecular Weight
- 35660.055 Da
References
- Hanley PJ, Ray J, Brandt U, Daut J: Halothane, isoflurane and sevoflurane inhibit NADH:ubiquinone oxidoreductase (complex I) of cardiac mitochondria. J Physiol. 2002 Nov 1;544(Pt 3):687-93. [Article]
- Kayser EB, Suthammarak W, Morgan PG, Sedensky MM: Isoflurane selectively inhibits distal mitochondrial complex I in Caenorhabditis elegans. Anesth Analg. 2011 Jun;112(6):1321-9. doi: 10.1213/ANE.0b013e3182121d37. Epub 2011 Apr 5. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway (PubMed:12707275, PubMed:16192278, PubMed:20439740, PubMed:21187401, PubMed:30923126). Within a catalytic cycle, acquires Ca(2+) or Mn(2+) ions on the cytoplasmic side of the membrane and delivers them to the lumenal side. The transfer of ions across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (PubMed:16192278, PubMed:16332677, PubMed:30923126). Plays a primary role in the maintenance of Ca(2+) homeostasis in the trans-Golgi compartment with a functional impact on Golgi and post-Golgi protein sorting as well as a structural impact on cisternae morphology (PubMed:14632183, PubMed:20439740). Responsible for loading the Golgi stores with Ca(2+) ions in keratinocytes, contributing to keratinocyte differentiation and epidermis integrity (PubMed:10615129, PubMed:14632183, PubMed:20439740). Participates in Ca(2+) and Mn(2+) ions uptake into the Golgi store of hippocampal neurons and regulates protein trafficking required for neural polarity (By similarity). May also play a role in the maintenance of Ca(2+) and Mn(2+) homeostasis and signaling in the cytosol while preventing cytotoxicity (PubMed:21187401)
- Specific Function
- Atp binding
Components:
References
- Kosk-Kosicka D: Plasma membrane Ca(2+)-ATPase as a target for volatile anesthetics. Adv Pharmacol. 1994;31:313-22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other/unknown
- General Function
- Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (PubMed:29478781). F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP turnover in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(1) domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits (PubMed:1531933)
- Specific Function
- Proton-transporting atp synthase activity, rotational mechanism
- Gene Name
- ATP5F1D
- Uniprot ID
- P30049
- Uniprot Name
- ATP synthase subunit delta, mitochondrial
- Molecular Weight
- 17489.755 Da
References
- Kosk-Kosicka D, Roszczynska G: Inhibition of plasma membrane Ca(2+)-ATPase activity by volatile anesthetics. Anesthesiology. 1993 Oct;79(4):774-80. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- Kharasch ED, Thummel KE: Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, and methoxyflurane. Anesthesiology. 1993 Oct;79(4):795-807. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- 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
- Sawas AH, Pentyala SN, Rebecchi MJ: Binding of volatile anesthetics to serum albumin: measurements of enthalpy and solvent contributions. Biochemistry. 2004 Oct 5;43(39):12675-85. [Article]
Drug created at June 13, 2005 13:24 / Updated at September 15, 2024 21:55