Effect of aminophylline upon the protective activity of common antiepileptic drugs and their plasma levels in mice.

Aminophylline (50 mg/kg) decreased the protective efficacy of carbamazepine (20 mg/kg), diphenylhydantoin (8-12 mg/kg), phenobarbital (20 and 25 mg/kg), and valproate (250 and 300 mg/kg) against electroconvulsions in mice. On the other hand, aminophylline (5 mg/kg) was devoid of such activity. Plasma levels of antiepileptic drugs were measured with the help of the Abbott TDx analyzer and after administration of carbamazepine (20 mg/kg), diphenylhydantoin (10 mg/kg), phenobarbital (25 mg/kg), and valproate (250 mg/kg) were as follows: 8.61, 6.48, 24.3 and 329 micrograms/ml, respectively. Aminophylline (50 mg/kg) remained without any significant influence upon these plasma levels. This may lead to the conclusion that aminophylline-induced reversal of antiepileptic drug activity is not dependent upon a pharmacokinetic mechanism and probably occurs at the neuronal level.