Tolperisone

Source: Wikipedia, the free encyclopedia.

Tolperisone
parenteral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
MetabolismLiver, kidney
Elimination half-life1st phase: 2 hrs
2nd phase: 12 hrs
ExcretionRenal
Identifiers
  • 2-methyl-1-(4-methylphenyl)-3-(1-piperidyl)propan-1-one
JSmol)
SMILES
  • C1CCCN(C1)CC(C(C2=CC=C(C=C2)C)=O)C
  • InChI=1S/C16H23NO/c1-13-6-8-15(9-7-13)16(18)14(2)12-17-10-4-3-5-11-17/h6-9,14H,3-5,10-12H2,1-2H3 ☒N
  • Key:FSKFPVLPFLJRQB-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Tolperisone (trade name Mydocalm among others) is a centrally acting

neurological diseases. It has been used since the 1960s.[1][2]

Medical uses

Tolperisone is indicated for use in the treatment of pathologically increased tone of the

encephalopathies manifested with muscular dystonia.[3][4]

Other possible uses include:[citation needed]

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.[3][4]

In 2012, following concerns about safety and efficacy, an "article 31 referral"[5] 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.[6]

Side effects

Adverse effects occur in fewer than 1% of patients and include muscle weakness, headache, arterial

anaphylactic shock.[3][7][8][9]

Overdose

Excitability has been noted after ingestion of high doses by children.[3] In suicide studies of three isolated cases, it is believed that ingestion of tolperisone was the cause of death.[10]

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.[3][4]

Pharmacology

Mechanism of action

Tolperisone is a centrally acting skeletal muscle relaxant that acts at the reticular formation in the brainstem[3] by blocking voltage-gated sodium and calcium channels.[11][12]

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.[3]

Chemistry

Tolperisone is a piperidine derivative.

Society and culture

Tolperisone was developed in the 1960s in Hungary.[2]

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. ^ "Tolperisone - referral | European Medicines Agency". www.ema.europa.eu. 22 June 2012. Retrieved 2024-03-04.
  2. ^
    PMID 18482024
    .
  3. ^
    ISBN 978-3-85200-181-4
    .
  4. ^ a b c d "Midocalm". Romania: InfoMedic. Archived from the original on 2014-07-30. Retrieved 2013-09-21.
  5. ^ "Referral procedures". European Medicines Agency. 17 September 2018. Retrieved 2022-11-20.
  6. ^ "Tolperisone". European Medicines Agency. 17 September 2018. Retrieved 2022-11-20.
  7. S2CID 24540050
    .
  8. PMID 14587432
    .
  9. PMID 21905508
    .
  10. PMID 21683537
    .
  11. S2CID 13020517
    .
  12. PMID 16650844
    .