The interaction between MK-801 and receptors for N-methyl-D-aspartate: functional consequences.
Electrophysiological studies using a cortical slice preparation revealed that MK-801 is a potent, non-competitive, antagonist of N-methyl-D-aspartate (NMDA)-induced depolarisations. Also, MK-801 was a highly selective antagonist, exhibiting a high degree of use-dependency. It completely blocked responses to NMDA and quinolinic acid but had no effect on responses produced by kainic acid or quisqualic acid. Using [3H]MK-801, high affinity binding sites for MK-801 were detected in membranes of the rat brain. The pharmacological specificity and regional distribution of binding sites for MK-801 were consistent with an action of the compound at the level of the NMDA receptor-associated ion channel. Administered parenterally, MK-801 had a remarkable neuroprotective role. It caused essentially complete protection against loss of neurones produced by injection of neurotoxic doses of NMDA or quinolinic acid into the striatum or hippocampus. Furthermore, MK-801 was highly effective in preventing loss of hippocampal neurones following bilateral occlusion of the common carotid arteries in the gerbil.
Woodruff
G N
GN
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
Foster
A C
AC
Gill
R
R
Kemp
J A
JA
Wong
E H
EH
Iversen
L L
LL
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D002540:Cerebral Cortex / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism; D017480:Receptors, sigma
D000777:Anesthetics; D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; C012134:SK&F 10047; D002795:Choline O-Acetyltransferase; D010620:Phenazocine