Is the site of action of ketamine anesthesia the N-methyl-D-aspartate receptor?
Synaptic mechanisms underlying ketamine anesthesia were studied using in vitro preparations of the lamprey CNS. Although lampreys are one of the most primitive vertebrates, the synaptic physiology and pharmacology are similar to those in the higher vertebrates. Axonal conduction, transmitter release from the presynaptic terminal, postsynaptic response to the putative neurotransmitters, and resting and activated membrane properties were studied in the absence and the presence of various concentrations of ketamine. Ketamine markedly reduced N-methyl-D-aspartate (NMDA)-activated responses, such as depolarizations to bath-applied NMDA and bursting rhythm during "fictive locomotion." The 50% block of the responses took place in the presence of 10-20 microM ketamine, whereas those induced by kainate and quisqualate (the other two subclasses of L-glutamate/L-aspartate agonists) were spared at concentrations higher than 600-800 microM. None of the other neuronal events tested were suppressed in the presence of still higher concentrations of ketamine. The results support the hypothesis that ketamine might exert its anesthetic effect by a pharmacologically specific interaction with the NMDA receptor.
Yamamura
T
T
Department of Anesthesiology, Hokkaido University School of Medicine, Sapporo, Japan.
Harada
K
K
Okamura
A
A
Kemmotsu
O
O
D000200:Action Potentials / Q000187:drug effects; D000758:Anesthesia; D000818:Animals; D004056:Differential Threshold; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007395:Interneurons / Q000502:physiology; D007649:Ketamine; D007798:Lampreys / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D012154:Reticular Formation / Q000166:cytology / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D007649:Ketamine