Source: Υπουργείο Υγείας (CY) Revision Year: 2020 Publisher: M. K. Stavrinos ltd., 3 Irakleous Str., 1046 Nicosia, Cyprus Tel.: 22434490, Fax: 22434485, E-mail: mkstavco@cytanet.com.cy
Pharmacotherapeutic group: muscle relaxants, centrally acting agents
ATC code: M03BX04
As a skeletal muscle relaxant whose prototype is mephenesine, tolperisone induces ataxia and muscle weakness in animal models by acting on the central nervous system at the spinal level. In fact it inhibits polysynaptic and monosynaptic reflexes with little action on non-reflex muscle response and without potentiating the phenobarbital sleep.
Since tolperisone and lidocaine have similar depressing effect on the activity of the fusimotor afferents and the structure of both molecules are similar, a same membrane stabilising action and a common receptor have been hypothesised.
To demonstrate the clinical efficacy to tolperisone, painful reflex muscle spasm was chosen as inclusion criteria in the main placebo-controlled double blind study. Deep muscle tenderness is a key feature of muscle spasm and can be assessed objectively by measurements of pain thresholds with a commercially available Pressure Tolerance Meter. As muscle spasm can involve neighbouring muscles as well as muscles farther away, sixteen standard pressure points were chosen in addition to the point with maximal pain. For each patient the sum of intraindividual differences at each time point in the study was calculated (a validated method), with the point of maximal pain contributing to 50% of the score. The change score of the pressure pain threshold during treatment with tolperisone increased to values significantly above those observed in therapy with placebo.
Tolperisone (INN).HCL (2,4' dimethyl-3-piperidino propiophenone hydrochloride) has a molecular mass of 281.8. The compound is water soluble.
Pharmacokinetics of tolperisone after administration of Mydoflex.
No pharmacokinetic studies were performed in renal failure and hepatic insufficiency. Nevertheless, in presence of hepatic insufficiency the diminished first pass effect can theoretically result in higher blood levels of tolperisone. As elimination is mainly renal, renal failure could result in higher blood levels of tolperisone metabolites (see §4.2).
High-fat meal increases the bioavailability of orally administered tolperisone by approx. 100% and increases the peak plasma concentration by approx. 45% as compared with fasting condition, delaying time to peak by approx. 30 minutes.
The LD50 in mice and rats is about 1400 mg/kg tolperisone hydrochloride (200 times the daily initial dose in human). Death results from respiratory paralysis.
The six month oral toxicity study in rats (50 mg/kg tolperisone hydrochloride given once a day) revealed no clinical or biological toxicity at doses at least seven times higher than the initial dose in human (6.9 mg/kg for a man of 65 kg, given in 3 divided doses).
The six month oral toxicity study in dogs (80 mg/kg tolperisone hydrochloride given once a day) revealed no clinical or biological toxicity at doses at least eleven times higher than the initial dose in human.
No embryo or foeto toxicity were revealed at 50 and 100 mg/kg tolperisone hydrochloride given orally in rabbit studies.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
