D,L-cis-2,3-Pyrrolidine dicarboxylate alters [3H]-L-glutamate binding and induces convulsions in mice.
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 microl) induced generalized tonic-clonic convulsions in mice in a dose-dependent manner. The coadministration of MK-801 (7 nmol/2.5 microl), with D,L-cis-2,3-PDC (16.5 nmol/2.5 microl), fully protected the animals against D,L-cis-2,3-PDC-induced convulsions, while the coadministration of DNQX (10 nmol/2.5 microl) 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.
Centro de Ciências Naturais e Exatas, Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Valéria Dornelles Gindri
VD
Sinhorin
Marcos José Souza
MJ
Carpes
Cheila
C
Roehrs
Melissa Freire
MF
Zimmer
Patricia Dutra
PD
Sauzem
Maribel Antonello
MA
Rubin
Carlos Roque Duarte
CR
Correia
Carlos Fernando
CF
Mello
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003292:Convulsants; D003998:Dicarboxylic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology; D011759:Pyrrolidines / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D003292:Convulsants; D003998:Dicarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011759:Pyrrolidines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C103758:pyrrolidine-2,3-dicarboxylic acid; D018698:Glutamic Acid; C056723:FG 9041; D016291:Dizocilpine Maleate