Differential Selectivity of Several Barbiturates on Experimental Seizures and Neurotoxicity in the Mouse
Differential Selectivity of Several Barbiturates on Experimental Seizures and Neurotoxicity in the Mouse
复制标题
几种巴比妥类药物对小鼠实验性癫痫发作和神经毒性的不同选择性
作者：
A. Raines;G. J. Blake;Bernice Richardson;Mark B. Gilbert
总结：评价了6种具有不同时间作用特征的巴比妥类药物-硫喷妥钠、戊巴比妥、丁巴比妥、苯巴比妥、二苯巴比妥和巴比妥-的“抗惊厥”和“神经毒性”作用。对于前者，采用MES试验、戊四唑90 mg/kg，s.c.诱发的阵挛性发作和戊四唑200 mg/kg，s.c.诱发的最大发作。对于后者，我们使用了旋转杆技术。MES试验中达到峰值活性的时间用作其他试验的时间。戊巴比妥至少需要神经毒性剂量才能产生实质性的“抗惊厥”活性，其保护指数在三次试验中的范围为0.79至0.98。在测试的药物中，苯巴比妥和苯巴比妥酸盐表现出最有利的保护指数，苯巴比妥从2.71到3.41，苯巴比妥从3.85到5.0。巴比妥是另一种作用持续时间较长的药物，其范围为0.84至2.81。虽然延长作用持续时间是抗癫痫活性的重要特征，但这种性质本身并不赋予有利的保护指数。
Summary: Six barbiturates with diverse time‐action characteristics– thiopental, pentobarbital, butabarbital, phenobarbital, diphenylbarbiturate, and barbital–were evaluated for “anticonvulsant” and “neurotoxic” effects. For the former, the MES test, clonic seizures induced by pentylenetetrazol, 90 mg/kg, s.c, and maximal seizures produced by pentylenetetrazol, 200 mg/kg, s.c, were employed. For the latter, we used a rotorod technique. Time to peak activity in the MES test was employed as the time for other tests. Pentobarbital required at least neurotoxic doses to produce substantial “anticonvulsant” activity, its protective index ranging from 0.79 to 0.98 in the three tests. Among the drugs tested, phenobarbital and diphenylbarbiturate exhibited the most favorable protective indices, ranging from 2.71 to 3.41 for phenobarbital and from 3.85 to 5.0 for diphenylbarbiturate. Barbital, another drug with a prolonged duration of action, exhibited a range from 0.84 to 2.81. Although a prolonged duration of action is an important characteristic for antiepileptic activity, this property does not confer per se a favorable protective index.