Disease relevance of Mydeton

• The efficacy and safety of oral tolperisone hydrochloride (Mydocalm) in the treatment of painful reflex muscle spasm was assessed in a prospective, randomized, double-blind, placebo-controlled trial [1].
• Whole-cell measurements in dorsal root ganglion cells revealed that tolperisone and silperisone depressed voltage-gated sodium channel conductance at concentrations that inhibited spinal reflexes [2].
• A randomized, double-blind, placebo-controlled study of the efficacy and safety of tolperisone in spasticity following cerebral stroke [3].
• Tolperisone given intravenously produced a transient hypotension, tachycardia, and hyperventilation [4].
• Together, these findings suggest that anaphylaxis to tolperisone is not uncommon and should be known to physicians in countries where this drug is available [5].

Psychiatry related information on Mydeton

• However, tolperisone hydrochloride proved to be significantly superior to placebo: the change score of the pressure pain threshold as the primary target parameter significantly increased during therapy with tolperisone hydrochloride (P = 0.03, valid-case-analysis) compared to the results obtained on placebo treatment [1].
• The present study substantiates clinical experience and previous clinical trials demonstrating that tolperisone hydrochloride, though being a centrally active muscle relaxant, does not cause any sedation and does not impair reaction times [6].

High impact information on Mydeton

• Isoform-specific cytochrome P450 (P450) inhibitors, inhibitory antibodies, and experiments with recombinant P450s pointed to CYP2D6 as the prominent enzyme in tolperisone metabolism [7].
• Therefore, it was concluded that tolperisone undergoes P450-dependent and P450-independent microsomal biotransformations to the same extent [7].
• Identification of metabolic pathways involved in the biotransformation of tolperisone by human microsomal enzymes [7].
• In the present study, head-dipping and place-learning (forms of nose-poking and spatial-preference tasks, respectively) paradigms with lateral hypothalamus stimulation were systematically analyzed using C57BL/6 mice in the presence and absence of two motor-deficit-inducing drugs: tolperisone and harmaline [8].
• Sedative effects of single and repeated doses of 50 mg and 150 mg tolperisone hydrochloride (Mydocalm), a centrally active muscle-relaxing agent, were evaluated in a placebo-controlled double-blind clinical trial [6].

Biological context of Mydeton

• Gas-liquid chromatographic method for the determination of tolperisone in human plasma: pharmacokinetic and comparative bioavailability studies [9].
• These results indicate that tolperisone shifts the blood volume from mesenteric (visceral) vessels to femoral (skeltal) ones [4].
• When injected directly into femoral and mesenteric arteries, tolperisone caused a rapid increase in both arterial flow (vasodilatation) [4].
• Mydocalm treatment of muscular and vascular complaints accompanying climacterics [10].
• We conclude that tolperisone (1) and lidocaine (2) despite their chemical divergence can still attach to identical protein binding sites [11].

Anatomical context of Mydeton

• Tolperisone (2.5-10 mg/kg) dose-dependently inhibited both ventral root reflexes and the dorsal root reflex [12].
• Tolperisone decreased the contractile force in an isolated and cross-circulated papillary muscle [4].
• The actions of tolperisone on single intact Ranvier nodes of the toad Xenopus were investigated by means of the Hodgkin-Huxley formalism [13].
• Coated Mydocalm tablet, known as striated muscle relaxant and peripheral vasodilator, has been used in climacteric women [10].
• Comparative characterisation of the centrally acting muscle relaxant RGH-5002 and tolperisone and of lidocaine based on their effects on rat spinal cord in vitro [14].

Associations of Mydeton with other chemical compounds

• In vivo, tolperisone and silperisone as well as lidocaine (10 mg/kg intravenously) depressed ventral root reflexes and excitability of motoneurons [2].
• Dantrolene, unlike tolperisone, a centrally acting muscle relaxant, dose-dependently inhibited twitch contraction evoked by electrical stimulation of both the muscle and the phrenic nerve in the rat isolated phrenic nerve-diaphragm preparation to a similar extent (IC50: 9.5 and 6.5 x 10(-6) M, respectively) [15].

Analytical, diagnostic and therapeutic context of Mydeton

• A stereoselective assay for the determination of tolperisone enantiomers in plasma by high performance liquid chromatography was developed [16].
• Treatment lasted 12 weeks and was started with a titration period of variable length (dose range 300-900 mg tolperisone daily) [3].
• Pharmacokinetic and comparative bioavailability studies were carried out after i.v. administration and after oral administration of two different preparations of tolperisone [9].
• HPLC determination of tolperisone in human plasma [17].

References