Effect of amlodipine upon the protective activity of antiepileptic drugs against maximal electroshock-induced seizures in mice.

Amlodipine, a calcium channel antagonist of the dihydropyridine class, up to 10 mg kg(-1)(i.p.) did not significantly affect the threshold for electroconvulsions. However, this calcium channel antagonist (10 mg kg(-1)) enhanced the anticonvulsive activity of carbamazepine, valproate and phenobarbital against maximal electroshock-induced seizures in mice. Furthermore, amlodipine (5 mg kg(-1)) intensified the protection offered by carbamazepine. This effect was associated with the increased free plasma level of carbamazepine in the presence of amlodipine. Amlodipine did not influence the free or total plasma level of phenobarbital and valproate, so a pharmacokinetic interaction is not probable for valproate and phenobarbital. The anticonvulsive action and free plasma level of diphenylhydantoin was not modified by amlodipine. The combined treatment of the calcium channel antagonist and antiepileptics caused motor impairment (evaluated in the chimney test). Long-term memory (assessed in the passive avoidance test) in case of combinations of amlodipine with carbamazepine or diphenylhydantoin was not affected. The combination of amlodipine with valproate or phenobarbital significantly influenced the retention in this test. A possible usefulness of amlodipine as add-on therapy in epileptic patients may be limited by its considerable adverse effect revealed by behavioural tests. The pharmacokinetic interaction between carbamazepine and amlodipine might have some clinical importance for patients treated with these drugs.