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

• Published in: Pharmacology, biochemistry and behavior Vol. 76; no. 2; pp. 295 - 299
• Main Authors: Sinhorin, Valéria Dornelles Gindri, Carpes, Marcos José Souza, Roehrs, Cheila, Zimmer, Melissa Freire, Sauzem, Patricia Dutra, Rubin, Maribel Antonello, Correia, Carlos Roque Duarte, Mello, Carlos Fernando
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2003; Elsevier Science
• Subjects: 2,3-Pyrrolidine dicarboxylate; Animals; Behavior, Animal - drug effects; Binding; Biological and medical sciences; Brain Chemistry - drug effects; Convulsants; Convulsion; Dicarboxylic Acids - antagonists & inhibitors; Dicarboxylic Acids - pharmacology; Dicarboxylic Acids - toxicity; Dizocilpine Maleate - pharmacology; DNQX; Excitatory Amino Acid Antagonists - pharmacology; Glutamate; Glutamatergic system (aspartate and other excitatory aminoacids); Glutamic Acid - metabolism; Intracerebroventricular administration; Male; Medical sciences; Membranes - drug effects; Membranes - metabolism; Mice; MK-801; Neuropharmacology; Neuroprotective Agents - pharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Pyrrolidines - antagonists & inhibitors; Pyrrolidines - pharmacology; Pyrrolidines - toxicity; Quinoxalines - pharmacology; Rats; Receptors, N-Methyl-D-Aspartate - drug effects; Seizures - chemically induced; Stereoisomerism; Structure-Activity Relationship; Binding; MK-801; DNQX; Intracerebroventricular administration; Convulsion; Glutamate; Stereoisomer; Rodentia; Central nervous system; Biological activity; Encephalon; Dose activity relation; Vertebrata; Mammalia; Binding capacity; Mouse; Analog; Animal; Plasma membrane; Intracerebral administration; Neurological disorder; Mechanism of action; NMDA receptor; Intracerebroventhcular administration
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2003.08.012

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.