Interaction of mu-opioid antagonistic drugs with antiepileptics

Interactions of the mu-opioid receptor antagonists, naloxone (0.3 and 1 mg/kg), cyprodime and clocinnamox (3 and 10 mg/kg for both drugs) with phenytoin (7 mg/kg), phenobarbital (7 mg/kg), carbamazepine (10 mg/kg) and valproic acid (130 mg/kg) were investigated using the electroconvulsive threshold in mice as a model in order to elucidate a possible role of mu-receptor mediated reactions in the mechanism of action of antiepileptic drugs. All 3 mu-antagonists are devoid of an effect on the electroconvulsive threshold. Pretreatment with the mu-antagonists resulted partly in an increase of anticonvulsant action, partly in a decrease, and partly the pretreatment had no effect on the electroconvulsive threshold. The anticonvulsant effect of phenytoin was antagonized dose-dependently by naloxone, that of phenobarbital by the dose of 10 mg/kg of clocinnamox. A common denominator of the mu-antagonistic interactions with anticonvulsants cannot be found and the effects observed are therefore considered as "unspecific".