THE COMPETITIVE NMDA ANTAGONIST, D-CPP-ENE, POTENTIATES THE ANTICONVULSANT ACTIVITY OF CONVENTIONAL ANTIEPILEPTICS AGAINST MAXIMAL ELECTROSHOCK-INDUCED SEIZURES IN MICE

D-CPP-ene (2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid; a c ompetitive antagonist of N-methyl-D-aspartic acid] in a dose of 2 mg/k g (i.p.) significantly increased the threshold for electroconvulsions. When given in a dose half that affecting the electroconvulsive thresh old, D-CPP-ene potentiated the anticonvulsant activity of carbamazepin e, diazepam, diphenylhydantoin, phenobarbital and valproate against ma ximal electroshock (50 mA)-induced seizures in mice. However, this NMD A antagonist did not influence the plasma levels of the antiepileptic drugs studied, so a pharmacokinetic interaction, in terms of total pla sma levels at least, is not probable. The chimney test and retention t esting in mice revealed that the combined treatment of D-CPP-ene at 1. 0 mg/kg (i.p.) with either diazepam, diphenylhydantoin, phenobarbital or valproate (providing a 50% protection against maximal electroshock convulsions) resulted in motor impairment and caused impairment of lon g-term memory, On the other hand, a combination of D-CPP-ene and carba mazepine was devoid of adverse effects. It can be concluded that the p otential utility of D-CPP-ene in combination with conventional antiepi leptic drugs does not seem promising, except for carbamazepine.