D, l- cis-2,3-Pyrrolidine dicarboxylate alters [ 3H]- l-glutamate binding and induces convulsions in mice

Abstract

This study investigated whether d, l- cis-2,3-Pyrrolidine dicarboxylate ( d, l- cis-2,3-PDC), a new glutamate analogue, alters glutamate binding to cerebral plasma membranes and whether N-methyl- d-aspartate (NMDA) receptors are involved in the convulsant effect of this compound. d, l- cis-2,3-PDC reduced sodium-independent [ 3H]- l-glutamate binding to lysed membrane preparations from adult rat cortex and had no effect on sodium-dependent glutamate binding. Intracerebroventricular administration of d, l- cis-2,3-PDC (7.5–25 nmol/5 μl) induced generalized tonic–clonic convulsions in mice in a dose-dependent manner. The coadministration of MK-801 (7 nmol/2.5 μl), with d, l- cis-2,3-PDC (16.5 nmol/2.5 μl), fully protected the animals against d, l- cis-2,3-PDC-induced convulsions, while the coadministration of DNQX (10 nmol/2.5 μl) increased the latency to convulsions but did not alter the percentage of animals that had convulsions. These results suggest that d, l- cis-2,3-PDC-induced effects are mediated predominantly by NMDA receptors.