Tolperisone

Tolperisone
Clinical data
Trade names	Mydocalm and others
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral, parenteral
ATC code	M02AX06 (WHO) M03BX04 (WHO);
Legal status
Legal status	In general: ℞ (Prescription only);
Pharmacokinetic data
Metabolism	Liver, kidney
Elimination half-life	1st phase: 2 hrs; 2nd phase: 12 hrs
Excretion	Renal
Identifiers
	IUPAC name 2-methyl-1-(4-methylphenyl)-3-(1-piperidyl)propan-1-one;
CAS Number	728-88-1 ;
PubChem CID	5511;
DrugBank	DB06264 ;
ChemSpider	5310 ;
UNII	F5EOM0LD8E;
KEGG	D08617 ;
ChEMBL	ChEMBL1076211 ;
CompTox Dashboard (EPA)	DTXSID8023686 ;
ECHA InfoCard	100.010.889
Chemical and physical data
Formula	C16H23NO
Molar mass	245.366 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CCCN(C1)CC(C(C2=CC=C(C=C2)C)=O)C;
	InChI 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 ; Key:FSKFPVLPFLJRQB-UHFFFAOYSA-N ;
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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.

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:

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 on the safety and efficacy, an "article 31 referral"[3] was triggered at the European Medicines Agency. The European Medicines Agency has recommended restricting the use of tolperisone. After review and a subsequent re-examination in 2012, the Agency concluded the safety and adverse reaction risks of this drug outweigh the benefits, and that there is weak support for its efficacy, in all but one indication (muscle stiffness or spasticity after stroke), and 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), their recommendations included ceasing advertising in Europe and ceasing injections, updating patient information leaflets, changing to another medicine for existing users, and for prescribers to only use it stroke patients when administered by mouth, not injection.[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 Mydocalm, Biocalm, Mydeton, Miderizone, Mydoflex, Myolax, Myoxan and Viveo.

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