Anticonvulsant drug potentiation by glycine in maximal electroshock seizures is mimicked by D-serine and antagonized by 7-chlorokynurenic acid.

This study evaluated a possible mechanism by which glycine potentiates the activity of anticonvulsant drugs against maximal electroshock seizures in rats. Administered concurrently, glycine (40 mmol/kg p.o.) significantly enhanced the anticonvulsant effect of phenobarbital, carbamazepine and phenytoin as determined by the occurrence of tonic hindlimb extension. Likewise, concurrent administration of the strychnine-insensitive glycine receptor agonist, D-serine (20 mmol/kg p.o.) significantly enhanced the anticonvulsant effect of phenobarbital, carbamazepine and phenytoin. L-Serine was ineffective. Administration of the strychnine-insensitive glycine receptor antagonist, 7-chlorokynurenic acid (100 nmol i.c.v.), significantly antagonized the potentiation of anticonvulsant activity induced by glycine co-administered with either phenobarbital or phenytoin. 7-Chlorokynurenic acid did not block tonic hindlimb extension when administered alone and did not affect the activity of the anticonvulsants in the absence of glycine. These results provide evidence for the potentiation of certain anticonvulsant drugs by glycine as a specific effect that may be mediated by the strychnine-insensitive glycine receptor.