Silperisone: A Centrally Acting Muscle Relaxant

Sándor Farkas
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引用次数: 20

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.

(1)
[ Chemical structure of silperisone. ]

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Silperisone:一种中枢作用的肌肉松弛剂
Silperisone是一种类似于tolperisone的有机硅化合物,具有中枢作用的肌肉松弛剂特性。对小鼠的研究表明,与托培力松或其他抗痉挛药物相比,silperisone引起中枢神经系统抑制或运动副作用的倾向较小。在猫和大鼠中,silperisone是一种有效的单突触和多突触脊髓反射和去脑性僵硬的抑制剂。其对脊髓反射的抑制作用也在离体半切大鼠脊髓中得到证实。静脉给药的体内效价和效果与托培力松和依培力松相似。然而,猫经十二指肠给药和小鼠经口服给药的作用时间比其他两种药物要长得多,其功能生物利用度也高得多。关于其作用概况silperisone与tolperisone相似,差异较小。最显著的差异是在脑桥促进和球抑制髌骨反射。托培力松抑制两者,而西尔培力松只抑制前者。silperisone脊髓反射抑制作用的机制涉及阻断电压门控神经元钠和钙通道,导致兴奋性递质释放减少,神经元兴奋性降低。此外,silperisone具有钾通道阻断作用,比tolperisone更强。Silperisone在大鼠体内吸收迅速,代谢广泛。然而,它在狗尤其是人类体内的代谢要少得多。silperisone在人体内的消除半衰期为12至16小时,因此可以每天给药一次或两次。在临床前试验中,剂量高达150mg /天的silperisone未能检测到血浆浓度被认为是有效的任何不良反应。这些发现表明,silperisone可能是一种有用的抗痉挛药物。然而,慢性动物毒性研究的发现导致了silperisone开发的中断。(1)[硅氧烷的化学结构。]]
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