Interactions of Anticonvulsants and Neuroleptics in Experimental Seizures

In general neuroleptics have no anticonvulsive properties but in contrast induce or enhance seizures (T.M. Itil and J.P. Meyers, in Anticonvulsant drugs, Vol. 2, p. 608, Pergamon press, 1973). Experimental data on the interactions of anticonvulsants with neuroleptics has not yet been found. Therefore we investigated in mice the effects of orally given melperone (mel), haloperidol (hal), chlorpromazine (cpz), and thioridazine (thi) separately and partially in combination with diphenylhydantoin (dph), dipropylacetate (dpa), trimethadione (tri) or diazepam (dia) using the min. and the max. electroshock seizure test (MinES, MES) and the max. pentetrazol seizure test (MPS). Only mel (a butyrophenone neuroleptic with sedative and weak anticonvulsive properties (Christensen et al., Acta pharmacol. et toxicol., 23, 109, 1965) showed anti-convulsive effects in all 3 tests (ED 50: 84; 53; 107 mg/kg resp.). CPZ was only effective in the MinES (ED 50: 57 mg/kg). Hal and thi were ineffective in all tests. The anticonvulsive action of dph was clearly diminished by all the neuroleptics tested in MES, resp. by mel tested in MPS. In contrast, the action of dia in MES and MPS was augmented. Combinations of mel with dia acted synergistic, those with mel and tri or dpa nearly additive against tonic seizures. The anticonvulsive action of dia, tri and dpa on clonic convulsions (MinES) was mostly augmented by the neuroleptics; antagonism was never found. The results show, that in mice neuroleptics have a antagonistic influence only on the antitonic antiepileptic dph. The anti-convulsive action of the also anticlonic active drugs dia, tri and dpa was either augmented by the neuroleptics or not influenced.