Differential effects of glycine on the anticonvulsant activity of D-cycloserine and L-701,324 in mice

The anticonvulsant effects of D-cycloserine, which is a partial agonist of the glycine/N-methyl-D-aspartate (NMDA) receptor, and L-701,324, which is a selective and potent antagonist that acts at the glycine site, were studied in electroshock-induced seizures in mice. Glycine, which is a natural full agonist that acts at the glycine site, enhanced the seizure threshold-increasing effect of D-cycloserine. L-701,324 produced a marked increase in the seizure threshold, which was significantly reversed by the administration of glycine. These results suggest that indirect glycine/NMDA antagonistic mechanisms may be responsible for the anticonvulsant action of D-cycloserine.