Effects of excitatory amino-acid antagonists on the anticonvulsant action of phenobarbital or diphenylhydantoin in mice.

The effects of L-glutamic acid diethyl ester (GDEE), D,L-alpha-aminoadipic acid (alpha-AA) and D,L-2-aminophosphonovaleric acid (APV) on the anticonvulsant action of phenobarbital and of diphenylhydantoin were studied in mice against electroconvulsions. Anticonvulsants were administered intraperitoneally 60 min and amino-acid antagonists 30 min before the test, by the same route. Neither GDEE (up to 400 mg/kg) nor alpha-AA (up to 100 mg/kg) were found to affect the seizure threshold whilst APV (100 and 200 mg/kg) raised the threshold moderately from 6.2 to 8.4 and 9.0 mA. APV and alpha-AA (up to 100 mg/kg) and GDEE (up to 400 mg/kg) did not affect the anticonvulsant potency of diphenylhydantoin. Only APV in the dose of 200 mg/kg potentiated the protective efficacy of this antiepileptic against maximal electroshock to a relatively low degree. The anticonvulsant action of phenobarbital was enhanced by APV (25-200 mg/kg) and alpha-AA in the dose of 50 but not in the dose of 100 mg/kg, GDEE being completely ineffective. These results suggest that the blockade of N-methyl-D-aspartic acid receptors by alpha-AA and APV is mainly responsible for the potentiation of the anticonvulsant activity of phenobarbital. The anticonvulsant effects of both antiepileptics do not seem to be related to the suppression by GDEE of events mediated by receptors for quisqualic acid.