Influence of melatonin upon the protective action of conventional anti-epileptic drugs against maximal electroshock in mice

Melatonin (50 mg/kg; 60 min before the test) significantly raised the electroconvulsive threshold in mice. The protective action of melatonin (50 mg/kg) in the electroconvulsive threshold test was reversed by aminophylline, picrotoxin and bicuculline. Melatonin at the subconvulsive dose of 25 mg/kg potentiated the anticonvulsive activity of carbamazepine and phenobarbital (ED50 values were significantly decreased from 12.1 to 8.3 and from 18.9 to 11.8 mg/kg, respectively). No potentiation was observed in the case of valproate and diphenylhydantoin (their ED(50)s were changed from 253 to 249 and from 10.3 to 9.7 mg/kg, respectively). Melatonin did not influence the plasma or brain levels of anti-epileptics studied, so a pharmacokinetic interaction is not probable. Melatonin (25 mg/kg) alone and its combinations with carbamazepine or phenobarbital, providing a 50% protection against maximal electroshock, were devoid of significant motor adverse effects, but caused strong long-term memory deficit. Consequently, it does not seem to be a good candidate for the treatment of epilepsy. (C) 1999 Elsevier Science B.V./ECNP All rights reserved.