Role of the NMDA receptor complex in DMCM-induced seizure in mice.
We investigated the role of the NMDA receptor complex in DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate)-induced seizures in mice. The seizure threshold of DMCM was evaluated using an i.v. infusion technique. Pretreatment with the non-competitive NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cycloheptan-5,10-imine maleate) or phencyclidine (PCP) significantly increased the seizure threshold for DMCM. Furthermore, the seizure threshold of DMCM was increased by intracerebroventricular (i.c.v.), but not intrathecal (i.t.), pretreatment with MK-801. Moreover, 7-chlorokynurenic acid, a glycine site antagonist, also increased the seizure threshold of DMCM, whereas ifenprodil, a non-competitive polyamine site antagonist, did not. These findings indicate that the ion-channel binding site and the glycine binding site on the NMDA receptor complex in the brain may be involved in the expression of seizures induced by DMCM.
Tsuda
M
M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Suzuki
T
T
Misawa
M
M
D000818:Animals; D002243:Carbolines / Q000008:administration & dosage; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D003292:Convulsants / Q000008:administration & dosage; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
D002243:Carbolines; D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; D010622:Phencyclidine; C010739:ifenprodil; C057013:7-chlorokynurenic acid