Differential Selectivity of Several Barbiturates on Experimental Seizures and Neurotoxicity in the Mouse

Abstract

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 [maximal electroshock seizure] 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 a rotorod technique was used. 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 3 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.