Interaction of famotidine, an H2 histamine receptor antagonist, with conventional antiepileptic drugs in mice

Abstract

H2 histamine receptors are localized postsynaptically in the CNS. The aim of this study was to evaluate the effects of acute (1 day) and prolonged (7 day) administration of the H2 histamine receptor antagonist, famotidine, on the anticonvulsant activity of conventional antiepileptic drugs (AEDs; valproate, carbamazepine, diphenylhydantoin and phenobarbital) against maximal electroshock (MES)-induced seizures in mice. In addition, the effects of these drugs alone or in combination with famotidine were studied on motor performance and long-term memory. The influence of H2 receptor antagonist on brain concentrations and free plasma levels of the antiepileptic drugs was also evaluated. After acute or prolonged administration of famotidine (at dose of 10mg/kg) the drug raised the threshold for electroconvulsions. No effect was observed on this parameter at lower doses. Famotidine (5mg/kg), given acutely, significantly enhanced the anticonvulsant activity of valproate, which was expressed by a decrease in ED50. After the 7-day treatment, famotidine (5mg/kg) increased the anticonvulsant activity of diphenylhydantoin against MES. Famotidine (5mg/kg), after acute and prolonged administration, combined with valproate, phenobarbital, diphenylhydantoin and carbamazepine did not alter their free plasma levels. In contrast, brain concentrations of valproate were elevated for 1-day treatment with famotidine (5mg/kg). Moreover, famotidine co-applied with AEDs, given prolonged, worsened motor coordination in mice treated with carbamazepine or diphenylhydantoin. In contrast this histamine antagonist, did not impair the performance of mice evaluated in the long-term memory task. The results of this study indicate that famotidine modifies the anticonvulsant activity of some antiepileptic drugs.