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Identification
- Summary
Thiocolchicoside is a semi-synthetic colchicine derivative used as an analgesic and anti-inflammatory.
- Generic Name
- Thiocolchicoside
- DrugBank Accession Number
- DB11582
- Background
Thiocolchicoside is a semi-synthetic derivative of the colchicine, a natural anti-inflammatory glycoside which originates from the flower seeds of Superba gloriosa. It is a muscle relaxant with anti-inflammatory and analgesic effects. It has potent convulsant activity and should not be administered to individuals prone to seizures.19
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Thiocolchicoside (DB11582)
- Weight
- Average: 563.62
Monoisotopic: 563.182517441 - Chemical Formula
- C27H33NO10S
- Synonyms
- TCC
- Thiocolchicine 2-glucoside analog
- Thiocolchicoside
- External IDs
- 210-017-7
Pharmacology
- Indication
Thiocolchicoside is a skeletal muscle-relaxant drug used in the treatment of orthopedic, traumatic and rheumatologic disorders 18. It is indicated as an adjuvant drug in the treatment of painful muscle contractures and is indicated in acute spinal pathology, for adults and adolescents 16 years of age and older 15. Recent studies have examined its effect on muscle tone, stiffness, contractures, and soreness experienced by athletes during sporting competitions 20.
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 Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination for symptomatic treatment of Back pain, acute Combination Product in combination with: Diclofenac (DB00586) •••••••••••• •••••• ••••••• ••••••• •••••••••••• Used in combination for symptomatic treatment of Chronic back pain Combination Product in combination with: Diclofenac (DB00586) •••••••••••• •••••• ••••••• ••••••• •••••••••••• Used in combination to manage Chronic back pain Combination Product in combination with: Etodolac (DB00749) •••••••••••• •••••• ••••••• ••••••• •••• •••••• Used in combination for symptomatic treatment of Extra-articular rheumatism Combination Product in combination with: Nimesulide (DB04743) •••••••••••• •••••• Used in combination for symptomatic treatment of Extra-articular rheumatism Combination Product in combination with: Nimesulide (DB04743) •••••••••••• ••• - Contraindications & Blackbox Warnings
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Thiocholchicoside is a muscle relaxing agent that works through selective binding to the GABA-A receptor. It prevents muscle contractions by activating the GABA inhibitory motor pathway 18.
This medication acts as a competitive GABA receptor antagonist and inhibits glycine receptors with similar potency as nicotinic acetylcholine receptors. It has powerful convulsant activity and should not be used in individuals at risk for seizures 18,23.
Used in combination with glafenine and meprobamate to tranquilize patients undergoing hysterosalpingography. In the treatment of painful muscle spasms. Thiocolchicoside acts both in contractures with a central cause and in contractures of reflex type, rheumatic and traumatic. It also alleviates symptoms of spastic sequelae of hemiparesis, Parkinson's disease and iatrogenic Parkinson symptoms, particularly neurodyslectic syndrome. Some other conditions that may benefit from this medication are acute and chronic lumbar and sciatic pain, cervico-brachial neuralgia, persistent torticollis, post-traumatic and post-operative pain 18.
- Mechanism of action
Thiocolchicoside, is a synthetic sulfur derivative of colchicoside, a naturally occurring glucoside contained in the Colchicum autumnale plant. Thiocolchicoside has a selective and potent affinity for g-aminobutyric acid A (GABA-A) receptors and acts on muscular contractures by activating the GABA inhibitory pathways thereby behaving as a potent muscle relaxant 18. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human cortex 11. GABAergic neurons are involved in myorelaxation, anxiolytic treatment, sedation, and anesthetics. GABA can also modulate heart rate and blood pressure.
It also has an affinity for the inhibitory glycine receptors (i.e., have glycomimetic and GABA mimetic activity), therefore acts as a muscle relaxant. Glycine is an inhibitory neurotransmitter and acts as an allosteric regulator of NMDA (N-methyl-D-aspartate) receptors. It is involved in the processing of motor and sensory data, thereby regulating movement, vision, and audition. Inhibitory neurotransmitter in spinal cord, allosteric regulator of NMDA receptors 19,12.
In one study, thiocolchicoside inhibited the function of recombinant human strychnine-sensitive glycine receptors composed of the alpha1 subunit with a potency (median inhibitory concentration of 47 microM) lower than that apparent with recombinant GABA(A) receptors. The drug also inhibited the function of human nicotinic acetylcholine receptors made of the alpha4 and beta2 subunits, however, this effect was partial and moreover only apparent at high concentrations. Thiocolchicoside demonstrated no effect on the function of 5-HT(3A) serotonin receptors 11.
Target Actions Organism AGamma-aminobutyric acid receptor subunit alpha-1 inhibitorHumans AGamma-aminobutyric acid receptor subunit beta-2 inhibitorHumans AGlycine receptor subunit alpha-2 inhibitorHumans AGlycine receptor subunit alpha-3 inhibitorHumans AGlycine receptor subunit beta inhibitorHumans AGamma-aminobutyric acid receptor subunit gamma-2 inhibitorHumans AGABA(A) Receptor antagonistHumans UGlycine receptor subunit alpha-1 antagonistHumans UTumor necrosis factor ligand superfamily member 11 antagonistHumans - Absorption
Oral bioavailability is ~25% After intramuscular administration, thiocolchicoside Cmax occur in 30 min and .reach values of 113 ng/mL after a 4 mg dose and 175 ng/mL after a 8 mg dose. The corresponding values of AUC are respectively 283 and 417 ng.h/mL. The pharmacologically active metabolite SL18.0740 is found at lower concentrations with a Cmax of 11.7 ng/mL occurring 5 h post administration and an AUC of 83 ng.h/mL 15.
After oral administration, no thiocolchicoside is detected in plasma. Only two metabolites are observed: The pharmacologically active metabolite SL18.0740 and an inactive metabolite SL59.0955. For both metabolites, maximum plasma concentrations occur 1hour after thiocolchicoside administration. After a single oral dose of 8 mg of thiocolchicoside the Cmax and AUC of SL18.0740 are about 60 ng/mL and 130 ng.h/mL respectively. For SL59.0955 these values are much lower: Cmax around 13 ng/mL and AUC ranging from 15.5 ng.h/mL (until 3h) to 39.7 ng.h/mL (until 24h) 15.
- Volume of distribution
The apparent volume of distribution of thiocolchicoside is estimated to be approximately 42.7 L after an intramuscular injection of 8 mg 15.
- Protein binding
The binding of 3H-colchicine and its derivative 3H-thiocolchicoside to human serum, purified human proteins, as well as red blood cells was studied using equilibrium dialysis and centrifugation. Binding of colchicine and thiocolchicoside to human serum was 38.9 C +/- 4.7 and 12.8 C +/- 5.3%, respectively, to albumin 7.
- Metabolism
Thiocolchicoside is rapidly absorbed after oral administration and metabolized into 3 main metabolites 18.
Firstly, in the intestines to 3-demethylcolchicine (inactive metabolite). This product is further metabolized in circulation by either conjugation to 3-O-glucurono-demethylcolchicine (active metabolite) or demethylated to didemethylcolchicine (inactive metabolite)
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- Route of elimination
Thiocolchicoside is not eliminated unchanged, rather as one of three metabolites found in either feces (~79 %) or in urine 20%. 3- demethylcolchicine (M2) and 3-O-glucurono-demethylcolchicine (M1) are found in both urine and feces, where as di-demethylcolchicine is found only in feces 24.
- Half-life
Approximately 7.7h 24.
- Clearance
Primarily extrarenal elimination (75% of the total body clearance) 13.
- 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
Has been shown to cause chromosomal aneuploidy and male infertility. Should be avoided during all stages of pregnancy, lactation and puberty. Is a potential risk factor for cancer.
In 2013, The European Medical Association (EMA) mandated that the use of thiocolchicoside-containing medicines by mouth or injection should be restricted across the European Union (EU). These drugs are now recommended only as an add-on treatment for painful muscle contractures resulting from spinal conditions in adults and adolescents 16 years old and older. Additionally, the dose of thiocolchicoside by mouth or injection should be limited. This is due to experimental evidence suggesting that thiocolchicoside was metabolized into M2 or SL59.0955, that has the propensity to damage dividing cells, resulting in aneuploidy (an abnormal number or arrangement of chromosomes). As a result, the CHMP (committee for medicinal products for human use) examined the safety profile of this medicine and consider what regulatory action might be appropriate 14.
The CHMP reviewed the evidence, with consideration of opinions from experts in medicines safety, and concluded that aneuploidy may occur with M2 at levels not significantly greater than those measured after recommended doses of thiocolchicoside ingested orally. Aneuploidy is a strong risk factor for fetal harm, decreased fertility in men, and could theoretically increase the risk of developing cancer 14.
The maximum recommended oral dose is 8 mg every 12 hours; treatment length should not exceed 7 consecutive days. When given intramuscularly (IM), the maximum dose is 4 mg every 12 hours, for a maximum of 5 days 14.
In addition to the above toxicity, a study was done on the hepatotoxic potential of thiocolchicoside. It was observed that serum AST and ALT levels increased following of the administration oral thiocolchicoside at 8 mg/day. Two weeks after discontinuing thiocolchicoside therapy, liver enzymes had decreased to levels within the normal range. Although infrequent, thiocolchicoside should be considered a rare hepatotoxic agent in clinical practice 10.
- Pathways
- Not Available
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Thiocolchicoside is combined with 1,2-Benzodiazepine. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Thiocolchicoside. Acetophenazine The risk or severity of CNS depression can be increased when Acetophenazine is combined with Thiocolchicoside. Agomelatine The risk or severity of CNS depression can be increased when Agomelatine is combined with Thiocolchicoside. Alfentanil The risk or severity of CNS depression can be increased when Alfentanil is combined with Thiocolchicoside. - Food Interactions
- Not Available
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.- International/Other Brands
- Biocolchid (Biogalenic) / Coltramyl / Coltrax / Eusilen (Velka) / Miorel / Musco-Ril / Muscoril / Myolax (Adwya) / Myoril / Neoflax / Neuroflax / TDP (Aamorb)
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image DEKSİT 12,5 MG/ML + 2,5 MG/ML DERİYE UYGULANACAK SPREY, ÇÖZELTİ 50 ML Thiocolchicoside (0.25 %) + Dexketoprofen trometamol (1.25 %) Spray Topical DROGSAN İLAÇLARI SAN. VE TİC. A.Ş. 2020-08-14 2021-10-04 Turkey 
DEKSİT 25 MG/4 MG TABLET Thiocolchicoside (4 mg) + Dexketoprofen (25 mg) Tablet DROGSAN İLAÇLARI SAN. VE TİC. A.Ş. 2017-12-21 Not applicable Turkey DEKSİT 25 MG/8 MG TABLET Thiocolchicoside (8 mg) + Dexketoprofen (25 mg) Tablet DROGSAN İLAÇLARI SAN. VE TİC. A.Ş. 2017-12-21 Not applicable Turkey DETROİTS 25 MG/4 MG FİLM KAPLI TABLET, 15 TABLET Thiocolchicoside (4 mg) + Dexketoprofen trometamol (25 mg) Tablet, coated Oral NEUTEC İLAÇ SAN. TİC. A.Ş. 2014-09-26 Not applicable Turkey DETROİTS 25 MG/4 MG FİLM KAPLI TABLET, 20 TABLET Thiocolchicoside (4 mg) + Dexketoprofen trometamol (25 mg) Tablet, coated Oral NEUTEC İLAÇ SAN. TİC. A.Ş. 2014-09-26 Not applicable Turkey - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ETOTIO 400 MG/8 MG FILM TABLET, 20 ADET Thiocolchicoside (8 mg) + Etodolac (400 mg) Tablet, film coated Oral GENSENTA İLAÇ SANAYİ VE TİC. A.Ş. 2017-05-02 Not applicable Turkey
Categories
- ATC Codes
- M03BX05 — Thiocolchicoside
- M03BX — Other centrally acting agents
- M03B — MUSCLE RELAXANTS, CENTRALLY ACTING AGENTS
- M03 — MUSCLE RELAXANTS
- M — MUSCULO-SKELETAL SYSTEM
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenolic glycosides. These are organic compounds containing a phenolic structure attached to a glycosyl moiety. Some examples of phenolic structures include lignans, and flavonoids. Among the sugar units found in natural glycosides are D-glucose, L-Fructose, and L rhamnose.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbohydrates and carbohydrate conjugates
- Direct Parent
- Phenolic glycosides
- Alternative Parents
- Hexoses / O-glycosyl compounds / Tropones / Anisoles / Alkyl aryl ethers / Alkylarylthioethers / Oxanes / Acetamides / Secondary carboxylic acid amides / Secondary alcohols show 9 more
- Substituents
- Acetal / Acetamide / Alcohol / Alkyl aryl ether / Alkylarylthioether / Anisole / Aromatic heteropolycyclic compound / Aryl thioether / Benzenoid / Carbonyl group show 24 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- T1X8S697GT
- CAS number
- 602-41-5
- InChI Key
- LEQAKWQJCITZNK-AXHKHJLKSA-N
- InChI
- InChI=1S/C27H33NO10S/c1-12(30)28-16-7-5-13-9-18(37-27-24(34)23(33)22(32)19(11-29)38-27)25(35-2)26(36-3)21(13)14-6-8-20(39-4)17(31)10-15(14)16/h6,8-10,16,19,22-24,27,29,32-34H,5,7,11H2,1-4H3,(H,28,30)/t16-,19+,22+,23-,24+,27+/m0/s1
- IUPAC Name
- N-[(10S)-3,4-dimethoxy-14-(methylsulfanyl)-13-oxo-5-{[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}tricyclo[9.5.0.0²,⁷]hexadeca-1(16),2,4,6,11,14-hexaen-10-yl]acetamide
- SMILES
- COC1=C(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C2CC[C@H](NC(C)=O)C3=CC(=O)C(SC)=CC=C3C2=C1OC
References
- General References
- Perucca E, Poitou P, Pifferi G: Comparative pharmacokinetics and bioavailability of two oral formulations of thiocolchicoside, a GABA-mimetic muscle relaxant drug, in normal volunteers. Eur J Drug Metab Pharmacokinet. 1995 Oct-Dec;20(4):301-5. [Article]
- Sandouk P, Bouvier d'Yvoire M, Chretien P, Tillement JP, Scherrmann JM: Single-dose bioavailability of oral and intramuscular thiocolchicoside in healthy volunteers. Biopharm Drug Dispos. 1994 Jan;15(1):87-92. [Article]
- Tuzun F, Unalan H, Oner N, Ozguzel H, Kirazli Y, Icagasioglu A, Kuran B, Tuzun S, Basar G: Multicenter, randomized, double-blinded, placebo-controlled trial of thiocolchicoside in acute low back pain. Joint Bone Spine. 2003 Sep;70(5):356-61. [Article]
- Ketenci A, Basat H, Esmaeilzadeh S: The efficacy of topical thiocolchicoside (Muscoril) in the treatment of acute cervical myofascial pain syndrome: a single-blind, randomized, prospective, phase IV clinical study. Agri. 2009 Jul;21(3):95-103. [Article]
- De Riu PL, Rosati G, Sotgiu S, Sechi G: Epileptic seizures after treatment with thiocolchicoside. Epilepsia. 2001 Aug;42(8):1084-6. [Article]
- Reuter S, Gupta SC, Phromnoi K, Aggarwal BB: Thiocolchicoside suppresses osteoclastogenesis induced by RANKL and cancer cells through inhibition of inflammatory pathways: a new use for an old drug. Br J Pharmacol. 2012 Apr;165(7):2127-39. doi: 10.1111/j.1476-5381.2011.01702.x. [Article]
- Sabouraud A, Chappey O, Dupin T, Scherrmann JM: Binding of colchicine and thiocolchicoside to human serum proteins and blood cells. Int J Clin Pharmacol Ther. 1994 Aug;32(8):429-32. [Article]
- Authors unspecified: Thiocolchicoside: review of adverse effects. Prescrire Int. 2016 Feb;25(168):41-3. [Article]
- Carta M, Murru L, Botta P, Talani G, Sechi G, De Riu P, Sanna E, Biggio G: The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system. Neuropharmacology. 2006 Sep;51(4):805-15. Epub 2006 Jun 30. [Article]
- Efe C, Purnak T, Ozaslan E, Milanlioglu A: Thiocolchicoside-induced liver injury. Clinics (Sao Paulo). 2011;66(3):521-2. [Article]
- Mascia MP, Bachis E, Obili N, Maciocco E, Cocco GA, Sechi GP, Biggio G: Thiocolchicoside inhibits the activity of various subtypes of recombinant GABA(A) receptors expressed in Xenopus laevis oocytes. Eur J Pharmacol. 2007 Mar 8;558(1-3):37-42. Epub 2006 Dec 12. [Article]
- Lopez-Corcuera B, Geerlings A, Aragon C: Glycine neurotransmitter transporters: an update. Mol Membr Biol. 2001 Jan-Mar;18(1):13-20. [Article]
- Sandouk P, Chappey O, d'Yvoire MB, Scherrmann JM: Pharmacokinetics of thiocolchicoside in humans using a specific radioimmunoassay. Ther Drug Monit. 1995 Oct;17(5):544-8. [Article]
- European Medicines Agency recommends restricting use of thiocolchicoside by mouth or injection [Link]
- Thiocolchicine EMA label [Link]
- Thiocolchicine Pubchem [Link]
- Thiocolchicine [Link]
- THIOCOLCHICOSIDE AS MUSCLE RELAXANT: A REVIEW [Link]
- To compare the efficacy and safety of fixed dose combination of thiocolchicoside and aceclofenac versus chlorzoxazone, aceclofenac and paracetamol in patients with acute lower backache associated with muscle spasm [Link]
- The effect of topical thiocolchicoside in preventing and reducing the increase of muscle tone, stiffness, and soreness: A real-life study on top-level road cyclists during stage competition [Link]
- Neurotransmitters as food supplements: the effects of GABA on brain and behavior [Link]
- GABA AND GLYCINE receptor modulators [Link]
- hiocolchicoside, 99% (HPLC) [Link]
- Review of the toxicology, pharmacodynamics and pharmacokinetics of thiocolchicoside, a GABA-agonist muscle relaxant with anti-inflammatory and analgesic actions [Link]
- MyHealthBox: Tiocolfen (thiocolchicide/ibuprofen) oral tablets [Link]
- TITCK Product Information: Adeleks (thiocolchicoside) oral tablets [Link]
- TITCK Product Information: Adeleks (thiocolchicoside) solution for intramuscular injection [Link]
- TITCK Product Information: Fixoline (thiocolchicoside) topical cream [Link]
- Ilac Prospektusu: Tyoflex (thiocolchicoside) topical ointment [Link]
- External Links
- KEGG Drug
- D07276
- PubChem Compound
- 9915886
- PubChem Substance
- 347827992
- ChemSpider
- 8091534
- BindingDB
- 233193
- 38085
- ChEBI
- 94557
- ChEMBL
- CHEMBL213907
- ZINC
- ZINC000004245665
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Thiocolchicoside
- MSDS
- Download (36.7 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 data4 Completed Treatment Back Pain Lower Back 1 somestatus stop reason just information to hide 4 Completed Treatment Myofascial Pain Syndrome 1 somestatus stop reason just information to hide 4 Completed Treatment Temporomandibular Disorders (TMD) 1 somestatus stop reason just information to hide 3 Completed Treatment Back Pain Lower Back 1 somestatus stop reason just information to hide 2 Active Not Recruiting Treatment Inflammatory Bowel Diseases (IBD) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Parenteral 4 mg Spray Topical Tablet Cream Topical Tablet, film coated Oral Syrup Oral Tablet Oral Cream Topical 0.25 % Injection, solution Intramuscular 4 mg Tablet, coated Oral 4 mg Tablet, coated Oral Gel Topical Powder, for solution Intramuscular Tablet, orally disintegrating Oral Tablet, orally disintegrating Oral 4 mg Capsule Oral Aerosol, foam Cutaneous Aerosol, foam Topical Injection Intramuscular Tablet, delayed release Oral Capsule, delayed release Oral Ointment Topical 75 mg Aerosol, foam Topical 0.25 % Capsule Oral 4 MG Capsule Oral 8 MG Tablet, orally disintegrating Oral 8 MG Capsule, coated Oral 8 mg Injection, solution Intramuscular 4 mg/2ml Cream Topical Cream Topical 2.5 MG/G Tablet, coated Oral 250 mg Tablet, coated Oral 8 mg Tablet, effervescent Oral Tablet, film coated Oral Ointment Topical 0.25 % Capsule, liquid filled Oral 4 mg Tablet, film coated Oral 4 mg Capsule, liquid filled Oral Tablet, effervescent Tablet Oral 8 mg Injection, solution Intramuscular 2 MG/ML Tablet Oral 4 mg Solution Intramuscular 4 mg Injection, solution Intramuscular 8 mg Tablet, coated Oral 800000 mg Capsule, coated Oral Capsule Oral Injection, solution Intramuscular Powder Oral Tablet Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 190-198 http://henankerui.lookchem.com/products/CasNo-602-41-5-Thiocolchicoside-12752892.html boiling point (°C) 929.624 http://henankerui.lookchem.com/products/CasNo-602-41-5-Thiocolchicoside-12752892.html water solubility 10 mg/mL https://www.sigmaaldrich.com/catalog/product/sigma/sml1476?lang=en®ion=CA logP 0.34 http://www2.unipr.it/~santipat/Posters/2003/tio2003.pdf pKa 12.74 https://www.ebi.ac.uk/chembldb/compound/inspect/CHEMBL1705373 - Predicted Properties
Property Value Source Water Solubility 0.348 mg/mL ALOGPS logP 0.78 ALOGPS logP -0.16 Chemaxon logS -3.2 ALOGPS pKa (Strongest Acidic) 12.2 Chemaxon pKa (Strongest Basic) -1.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 164.01 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 145.06 m3·mol-1 Chemaxon Polarizability 57.72 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 234.7461909 predictedDarkChem Lite v0.1.0 [M-H]- 220.37257 predictedDeepCCS 1.0 (2019) [M+H]+ 232.8561909 predictedDarkChem Lite v0.1.0 [M+H]+ 222.2072 predictedDeepCCS 1.0 (2019) [M+Na]+ 233.5359909 predictedDarkChem Lite v0.1.0 [M+Na]+ 227.81302 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
- Gene Name
- GABRA1
- Uniprot ID
- P14867
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-1
- Molecular Weight
- 51801.395 Da
References
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:19763268, PubMed:27789573, PubMed:29950725, PubMed:8264558). 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). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (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). Extrasynaptic beta-2 receptors contribute to the tonic GABAergic inhibition (By similarity). Beta-containing GABAARs can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness (By similarity)
- Specific Function
- Chloride channel activity
- Gene Name
- GABRB2
- Uniprot ID
- P47870
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit beta-2
- Molecular Weight
- 59149.895 Da
References
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:15302677, PubMed:16144831, PubMed:2155780, PubMed:23895467, PubMed:25445488, PubMed:26370147, PubMed:34473954). Channel opening is also triggered by taurine and beta-alanine (PubMed:15302677). Plays a role in synaptic plasticity (By similarity). Contributes to the generation of inhibitory postsynaptic currents, and is involved in the down-regulation of neuronal excitability (PubMed:25445488). Plays a role in cellular responses to ethanol (PubMed:23895467)
- Specific Function
- Extracellularly glycine-gated chloride channel activity
- Gene Name
- GLRA2
- Uniprot ID
- P23416
- Uniprot Name
- Glycine receptor subunit alpha-2
- Molecular Weight
- 52001.585 Da
References
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:26416729, PubMed:9677400). Channel characteristics depend on the subunit composition; heteropentameric channels display faster channel closure (By similarity). Plays an important role in the down-regulation of neuronal excitability (By similarity). Contributes to the generation of inhibitory postsynaptic currents (By similarity). Contributes to increased pain perception in response to increased prostaglandin E2 levels (By similarity). Plays a role in cellular responses to ethanol (By similarity)
- Specific Function
- Extracellularly glycine-gated chloride channel activity
- Gene Name
- GLRA3
- Uniprot ID
- O75311
- Uniprot Name
- Glycine receptor subunit alpha-3
- Molecular Weight
- 53799.775 Da
References
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Glycine receptors are ligand-gated chloride channels. GLRB does not form ligand-gated ion channels by itself, but is part of heteromeric ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:11929858, PubMed:15302677, PubMed:16144831, PubMed:22715885, PubMed:23238346, PubMed:25445488, PubMed:34473954, PubMed:8717357). Heteropentameric channels composed of GLRB and GLRA1 are activated by lower glycine levels than homopentameric GLRA1 (PubMed:8717357). Plays an important role in the down-regulation of neuronal excitability (PubMed:11929858, PubMed:23238346). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488)
- Specific Function
- Extracellularly glycine-gated chloride channel activity
- Gene Name
- GLRB
- Uniprot ID
- P48167
- Uniprot Name
- Glycine receptor subunit beta
- Molecular Weight
- 56121.62 Da
References
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Gamma subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:14993607, PubMed:16412217, PubMed:23909897, PubMed:2538761, PubMed:25489750, PubMed:27864268, 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:14993607, PubMed:16412217, PubMed:2538761, PubMed:27864268, PubMed:29950725, PubMed:30602789). Gamma-2/GABRG2-containing GABAARs are found at both synaptic and extrasynaptic sites (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). Extrasynaptic gamma-2-containing receptors contribute to the tonic GABAergic inhibition (By similarity). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response in a gamma-2 subunit-controlled manner (By similarity)
- Specific Function
- Benzodiazepine receptor activity
- Gene Name
- GABRG2
- Uniprot ID
- P18507
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit gamma-2
- Molecular Weight
- 55185.07 Da
References
- 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]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- 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
- Carta M, Murru L, Botta P, Talani G, Sechi G, De Riu P, Sanna E, Biggio G: The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system. Neuropharmacology. 2006 Sep;51(4):805-15. Epub 2006 Jun 30. [Article]
- Mascia MP, Bachis E, Obili N, Maciocco E, Cocco GA, Sechi GP, Biggio G: Thiocolchicoside inhibits the activity of various subtypes of recombinant GABA(A) receptors expressed in Xenopus laevis oocytes. Eur J Pharmacol. 2007 Mar 8;558(1-3):37-42. Epub 2006 Dec 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- 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
- Mascia MP, Bachis E, Obili N, Maciocco E, Cocco GA, Sechi GP, Biggio G: Thiocolchicoside inhibits the activity of various subtypes of recombinant GABA(A) receptors expressed in Xenopus laevis oocytes. Eur J Pharmacol. 2007 Mar 8;558(1-3):37-42. Epub 2006 Dec 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy (PubMed:22664871). Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation (By similarity)
- Specific Function
- Cytokine activity
- Gene Name
- TNFSF11
- Uniprot ID
- O14788
- Uniprot Name
- Tumor necrosis factor ligand superfamily member 11
- Molecular Weight
- 35477.81 Da
References
- Reuter S, Gupta SC, Phromnoi K, Aggarwal BB: Thiocolchicoside suppresses osteoclastogenesis induced by RANKL and cancer cells through inhibition of inflammatory pathways: a new use for an old drug. Br J Pharmacol. 2012 Apr;165(7):2127-39. doi: 10.1111/j.1476-5381.2011.01702.x. [Article]
Drug created at April 23, 2016 14:19 / Updated at August 26, 2024 19:24