Silperisone: a centrally acting muscle relaxant

Abstract

Silperisone is a tolperisone like organosilicon compound with centrally acting muscle relaxant properties. Studies in mice showed that silperisone may have less propensity to cause CNS depressant or motor side effects than tolperisone or other antispastic drugs. In cats and rats, silperisone was an effective suppressant of monosynaptic and polysynaptic spinal reflexes and decerebrate rigidity. Its suppressant effect on the spinal reflexes was also demonstrated in the isolated hemisected rat spinal cord in vitro. The in vivo potency and efficacy of silperisone by i.v administration were similar to those of tolperisone and eperisone. However, in cats by intraduodenal administration and in mice by oral administration its duration of action was much longer and its functional bioavailability much higher than of the other two drugs. With regard to its profile of actions silperisone was similar to tolperisone with minor differences. The most striking difference was in pontine facilitation and bulbar inhibition of the patellar reflex. Tolperisone depressed both, whereas silperisone inhibited only the former. The mechanism underlying the spinal reflex depressant effects of silperisone involves the blockade of voltage gated neuronal sodium and calcium channels leading to a decreased release of excitatory transmitter and reduced neuronal excitability. In addition, silperisone has potassium channel blocking effect, which is stronger than that of tolperisone. Silperisone is absorbed rapidly and is extensively metabolized in rats. However, its metabolism in dogs and particularly in humans is much less extensive. The elimination half-life of silperisone in humans is 12 to 16 h, so that it can be administered once or twice daily. Phase I clinical studies with silperisone at doses up to 150 mg/day failed to detect any adverse effects at plasma concentrations considered to be effective in the preclinical tests. These findings suggested that silperisone might be a useful antispastic drug. However, findings in chronic animal toxicity studies led to the discontinuation of silperisone's development.