Inhibitory effects of NMDA receptor antagonists on hypoxia-induced seizures in dietary Mg(2+)-deficient mice.
The effects of the non-competitive N-methyl-D-aspartate (NMDA) antagonists, (+)-MK-801 hydrogen maleate (MK-801) and phencyclidine hydrochloride (PCP), were tested against hypoxia-induced tonic convulsions and hippocampal epileptiform discharges. Systemic administration of MK-801 and PCP suppressed the hypoxia-induced tonic convulsions in dietary Mg(2+)-deficient mice in a dose-dependent manner. The ED50 values (and their 95% confidence limits) of MK-801 and PCP were 0.19 (0.14-0.26) and 1.14 (0.32-4.11) mumol/kg, respectively. These values were lower than those of the conventional anticonvulsants tested. Induction of epileptiform discharges following hypoxia was also prevented by the presence of MK-801 and PCP at concentrations of 5-30 microM. The hypoxia-induced epileptiform discharges, however, were reduced, but not blocked completely, by the application of MK-801 and PCP. These results strongly suggest that activation of NMDA receptors in the hippocampus plays a pivotal role in the induction of hypoxia-induced tonic convulsions in dietary Mg(2+)-deficient mice.
Nakanishi
H
H
Department of Pharmacology, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
Kamata
O
O
Ukai
K
K
Yamamoto
K
K
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000648:ultrastructure; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008275:Magnesium Deficiency / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D010622:Phencyclidine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology
D000927:Anticonvulsants; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D010622:Phencyclidine