Тиозид 4 , Таблетки

Форма выпуска и состав

Лекарственный препарат Muscoflex поступает в продажу в форме капсул и раствора для инъекций в ампулах.

Капсулы покрыты пищевым желатином и расфасованы в блистеры по 10 шт. в каждом. В фирменной картонной коробке упакованы 2 блистера, 20 капсул. Каждая единица содержит 4 мг активного вещества (тиоколхикозида).

В состав медикамента входят вспомогательные вещества:

• лактозы моногидрат;
• кукурузный крахмал;
• магния стеарат.

Срок годности капсул составляет 3 года с даты изготовления, которая выдавлена на блистерах. Цена упаковки лекарства варьируется в пределах 76–110 рублей в зависимости от статуса аптеки и региона. Российские аналоги (Артоксан, Артикард, Окситен) имеют практически одинаковую стоимость с турецким препаратом, но таблетки могут быть выписаны бесплатно в рамках одной из действующих программ.

Раствор для инъекций заключен в прозрачные стеклянные ампулы емкостью 2 мл.

В каждой ампуле содержатся такие компоненты:

• тиоколхикозид;
• хлорид натрия;
• вода для инъекций.

Ампулы расфасованы в картонные контейнеры по 6 шт. Раствор представляет собой прозрачную маслянистую жидкость с желтоватым оттенком. Контейнеры и инструкция по применению упакованы в фирменную картонную коробку, на которую нанесено название, штрихкод, реквизиты производителя и основные предостережения. Срок годности раствора – 2 года. Цена упаковки варьируется в пределах 72–96 рублей.

Хранить медикамент нужно в темном, защищенном от света и недоступном для детей месте при температуре +12–25°C.

Side effects

Side effects of thiocolchicoside can include nausea, allergy and vasovagal reactions.
Liver injury, pancreatitis, seizures, blood cell disorders, severe cutaneous disorders, rhabdomyolysis, and reproductive disorders have all been recorded in the French and European pharmacovigilance databases and in the periodic updates that the companies concerned submit to regulatory agencies. These data do not specify the frequency of the disorders nor do they identify the most susceptible patient populations. Thiocolchicoside is teratogenic in experimental animals and also damages chromosomes. Human data are limited to a follow-up of about 30 pregnant women (no major malformations) and reports of altered spermatogenesis, including cases of azoospermia. In practice, there is no justification for exposing patients to the adverse effects of thiocolchicoside. It is better to use an effective, well-known analgesic for patients complaining of muscle pain, starting with paracetamol.

Although muscle relaxants may have the major side effect of sedation, thiocolchicoside is free from sedation effects possible due to non-interference with nicotinic receptors.

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&region=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
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	12.2
pKa (Strongest Basic)	-1.2
Physiological Charge
Hydrogen Acceptor Count	10
Hydrogen Donor Count	5
Polar Surface Area	164.01 Å2
Rotatable Bond Count	7
Refractivity	145.06 m3·mol-1
Polarizability	57.72 Å3
Number of Rings	4
Bioavailability	1
Rule of Five	No
Ghose Filter	No
Veber’s Rule	No
MDDR-like Rule	Yes

Predicted ADMET features

Not Available

Identification

Name

Thiocolchicoside

Accession Number

DB11582

Type

Small Molecule

Groups

Experimental

Description

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 .

Structure

Synonyms

• TCC
• Thiocolchicine 2-glucoside analog

External IDs

210-017-7

International/Other Brands

Biocolchid (Biogalenic)ColtramylColtraxEusilen (Velka)MiorelMusco-RilMuscorilMyolax (Adwya)MyorilNeoflaxNeuroflaxTDP (Aamorb)

Categories

• Alkaloids
• Central Nervous System Depressants
• Muscle Relaxants
• Muscle Relaxants, Centrally Acting Agents
• Musculo-Skeletal System

UNII

T1X8S697GT

CAS number

602-41-5

Weight

Average: 563.62 Monoisotopic: 563.182517441

Chemical Formula

C₂₇H₃₃NO₁₀S

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-oxy}tricyclohexadeca-1(16),2,4,6,11,14-hexaen-10-yl]acetamide

SMILES

COC1=C(O2O(CO)(O)(O)2O)C=C2CC(NC(C)=O)C3=CC(=O)C(SC)=CC=C3C2=C1OC

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum — 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum — 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum — 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum — 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum — 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum — 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

References

General References

1. 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.
2. 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.
3. 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.
4. 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.
5. De Riu PL, Rosati G, Sotgiu S, Sechi G: Epileptic seizures after treatment with thiocolchicoside. Epilepsia. 2001 Aug;42(8):1084-6.
6. 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.
7. 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.
8. Authors unspecified: Thiocolchicoside: review of adverse effects. Prescrire Int. 2016 Feb;25(168):41-3.
9. 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.
10. Efe C, Purnak T, Ozaslan E, Milanlioglu A: Thiocolchicoside-induced liver injury. Clinics (Sao Paulo). 2011;66(3):521-2.
11. 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.
12. Lopez-Corcuera B, Geerlings A, Aragon C: Glycine neurotransmitter transporters: an update. Mol Membr Biol. 2001 Jan-Mar;18(1):13-20.
13. 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.
14. European Medicines Agency recommends restricting use of thiocolchicoside by mouth or injection
15. Thiocolchicine EMA label
16. Thiocolchicine Pubchem
17. Thiocolchicine
18. THIOCOLCHICOSIDE AS MUSCLE RELAXANT: A REVIEW
19. 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
20. 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
21. Neurotransmitters as food supplements: the effects of GABA on brain and behavior
22. GABA AND GLYCINE receptor modulators
23. hiocolchicoside, 99% (HPLC)
24. Review of the toxicology, pharmacodynamics and pharmacokinetics of thiocolchicoside, a GABA-agonist muscle relaxant with anti-inflammatory and analgesic actions

External Links

KEGG Drug

D07276

PubChem Compound

PubChem Substance

ChemSpider

BindingDB

ChEBI

ChEMBL

CHEMBL213907

Drugs.com

Drugs.com Drug Page

Wikipedia

Thiocolchicoside

ATC Codes

M03BX05 — Thiocolchicoside

• M03BX — Other centrally acting agents
• M03B — MUSCLE RELAXANTS, CENTRALLY ACTING AGENTS
• M03 — MUSCLE RELAXANTS
• M — MUSCULO-SKELETAL SYSTEM

M03BX55 — Thiocolchicoside, combinations

• M03BX — Other centrally acting agents
• M03B — MUSCLE RELAXANTS, CENTRALLY ACTING AGENTS
• M03 — MUSCLE RELAXANTS
• M — MUSCULO-SKELETAL SYSTEM

MSDS

Download (36.7 KB)

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
Unlock Additional Data
2,5-Dimethoxy-4-ethylthioamphetamine	The risk or severity of adverse effects can be increased when Thiocolchicoside is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine	The risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Thiocolchicoside.
4-Methoxyamphetamine	The risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Thiocolchicoside.
5-methoxy-N,N-dimethyltryptamine	The risk or severity of adverse effects can be increased when Thiocolchicoside is combined with 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole	The risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Thiocolchicoside.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline	The risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Thiocolchicoside.
Acepromazine	The risk or severity of adverse effects can be increased when Acepromazine is combined with Thiocolchicoside.
Aceprometazine	The risk or severity of adverse effects can be increased when Aceprometazine is combined with Thiocolchicoside.
Acetazolamide	The risk or severity of adverse effects can be increased when Acetazolamide is combined with Thiocolchicoside.
Acetophenazine	The risk or severity of adverse effects can be increased when Acetophenazine is combined with Thiocolchicoside.

Additional Data Available

• Extended Description

  Extended Description

  Extended description of the mechanism of action and particular properties of each drug interaction.

  Learn more

• Severity

  Severity

  A severity rating for each drug interaction, from minor to major.

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• Evidence Level

  Evidence Level

  A rating for the strength of the evidence supporting each drug interaction.

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• Action

  Action

  An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Not Available

References

1. ^
2. Soonawalla DF, Joshi N (May 2008). «Efficacy of thiocolchicoside in Indian patients suffering from low back pain associated with muscle spasm». Journal of the Indian Medical Association. 106 (5): 331–5.  .
3. «Thiocolchicoside: review of adverse effects». Prescrire International. 25 (168): 41–3. February 2016.  .