Chemistry:Tolperisone
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| Trade names | Mydocalm and others |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | Oral, parenteral |
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| Pharmacokinetic data | |
| Metabolism | Liver, kidney |
| Elimination half-life | 1st phase: 2 hrs 2nd phase: 12 hrs |
| Excretion | Renal |
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| Formula | C16H23NO |
| Molar mass | 245.366 g·mol−1 |
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Tolperisone (trade name Mydocalm among others) is a centrally acting skeletal muscle relaxant used for the treatment of increased muscle tone associated with neurological diseases. It has been used since the 1960s.[citation needed]
Medical uses
Tolperisone is indicated for use in the treatment of pathologically increased tone of the skeletal muscle caused by neurological diseases (damage of the pyramidal tract, multiple sclerosis, myelopathy, encephalomyelitis) and of spastic paralysis and other encephalopathies manifested with muscular dystonia.[1][2]
Other possible uses include:[citation needed]
- Spondylosis
- Spondylarthrosis
- Cervical and lumbar syndromes
- Arthrosis of the large joints
- Obliterating atherosclerosis of the extremity vessels
- Diabetic angiopathy
- Thromboangiitis obliterans
- Raynaud's syndrome
Contraindications and cautions
Manufacturers report that tolperisone should not be used in patients with myasthenia gravis. Only limited data are available regarding the safety in children, youths, during pregnancy and breastfeeding. It is not known whether tolperisone is excreted into mother's milk.[1][2]
In 2012, following concerns about safety and efficacy, an "article 31 referral"[3] was triggered at the European Medicines Agency (EMA). After the review and a subsequent re-examination, the Agency concluded that the benefits of tolperisone-containing medicines given orally continue to outweigh their risks. However, there is weak support for tolperisone's efficacy, specifically due to the prevalence of hypersensitivity symptoms such as flushing, rash, severe skin itchiness (with raised lumps), wheezing, difficulty breathing and swallowing, fast heartbeat, and fast decrease in blood pressure (basically anaphylaxis). The EMA recommends that tolperisone use be restricted to the treatment of adults with post-stroke spasticity (stiffness). The EMA also advises cessation of advertising, only using tolperisone orally, updating patient information leaflets, and changing to another medicine for existing users.[4]
Side effects
Adverse effects occur in fewer than 1% of patients and include muscle weakness, headache, arterial hypotension, nausea, vomiting, dyspepsia, and dry mouth. All effects are reversible.[1][2] Allergic reactions occur in fewer than 0.1% of patient and include skin rash, hives, Quincke's edema, and in some cases anaphylactic shock.[1][5][6][7]
Overdose
Excitability has been noted after ingestion of high doses by children.[1] In suicide studies of three isolated cases, it is believed that ingestion of tolperisone was the cause of death.[8]
Interactions
Tolperisone does not have a significant potential for interactions with other pharmaceutical drugs. It cannot be excluded that combination with other centrally acting muscle relaxants, benzodiazepines or nonsteroidal anti-inflammatory drugs (NSAIDs) may make a dose reduction necessary in some patients.[1][2]
Pharmacology
Mechanism of action
Tolperisone is a centrally acting muscle relaxant that acts at the reticular formation in the brain stem[1] by blocking voltage-gated sodium and calcium channels.[9][10]
Pharmacokinetics
Tolperisone is absorbed nearly completely from the gut and reaches its peak blood plasma concentration after 1.5 hours. It is extensively metabolised in the liver and kidneys. The substance is excreted via the kidneys in two phases; the first with a half-life of two hours, and the second with a half-life of 12 hours.[1]
Chemistry
Tolperisone a piperidine derivative.
Society and culture
Brand names
Brand names include Biocalm, Miderizone, Mydeton, Mydocalm, Mydoflex, Myolax, Myoxan, Tolson, Topee, and Viveo.
See also
Chemically and mechanistically related drugs:
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 (in de) Austria-Codex (62nd ed.). Vienna: Österreichischer Apothekerverlag. 2007. pp. 5510–1. ISBN 978-3-85200-181-4.
- ↑ 2.0 2.1 2.2 2.3 "Midocalm". Romania: InfoMedic. http://www.info-medic.ro/midocalm/.
- ↑ "Referral procedures". 17 September 2018. https://www.ema.europa.eu/en/human-regulatory/post-authorisation/referral-procedures.
- ↑ "Tolperisone". 17 September 2018. https://www.ema.europa.eu/en/medicines/human/referrals/tolperisone.
- ↑ "Anaphylactic reactions to tolperisone (Mydocalm)". Swiss Medical Weekly 133 (25–26): 369–371. June 2003. doi:10.4414/smw.2003.10280. PMID 12947534.
- ↑ "[Mydocalm causing anaphylaxis]" (in pl). Pneumonologia I Alergologia Polska 71 (5–6): 250–252. 2003. PMID 14587432.
- ↑ "An immediate hypersensitivity reaction caused by tolperisone hydrochloride". Journal of Investigational Allergology & Clinical Immunology 21 (5): 411–412. 2011. PMID 21905508.
- ↑ "Fatal tolperisone poisoning: autopsy and toxicology findings in three suicide cases". Forensic Science International 215 (1–3): 101–104. February 2012. doi:10.1016/j.forsciint.2011.05.025. PMID 21683537.
- ↑ "Tolperisone-type drugs inhibit spinal reflexes via blockade of voltage-gated sodium and calcium channels". The Journal of Pharmacology and Experimental Therapeutics 315 (3): 1237–1246. December 2005. doi:10.1124/jpet.105.089805. PMID 16126840.
- ↑ "A comparative study of the action of tolperisone on seven different voltage dependent sodium channel isoforms". European Journal of Pharmacology 538 (1–3): 5–14. May 2006. doi:10.1016/j.ejphar.2006.03.034. PMID 16650844.
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