title: [NMDA receptor antagonist neurotoxicity and psychotomimetic activity].
abstract: Non-competitive NMDA receptor antagonists, in spite of their neuroprotective effects against neuronal ischemia, brain trauma, etc., cause neuronal damage in the rodent posterior cingulate and retrosplenial cortices (PC/RS), which are thought to be responsible brain regions for their psychotomimetic activity in humans. A number of anesthetics have not only GABAA receptor activating properties but also NMDA receptor antagonist properties. On the other hand, ketamine and nitrous oxide, both of which are potent non-competitive NMDA receptor antagonists and have little GABAA activating properties, are demonstrated to induce neuronal damage in the rat PC/RS. Furthermore, ketamine potentiates the neuronal damage by nitrous oxide. Although many anesthetics, such as halothane, isoflurane, barbiturates and benzodiazepines, inhibit the neuronal damage in the PC/RS by NMDA receptor antagonists, probably through GABAA receptor activation, we anesthesiologists should be aware of the risk of ketamine or nitrous oxide anesthesia, not to speak of the combined use of them, without using GABAA receptor activating agents.
authors.affiliation: Department of Anesthesiology, Kansai Medical University, Moriguchi 570-8507.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakao
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagata
authors.forename: Munehiro
authors.initials: M
authors.lastname: Masuzawa
authors.forename: Etsuko
authors.initials: E
authors.lastname: Miyamoto
authors.forename: Makiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Nishizawa
authors.forename: Koh
authors.initials: K
authors.lastname: Shingu
mesh_terms: D000778:Anesthetics, Dissociative / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D018757:GABA Modulators / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000187:drug effects; D006212:Hallucinations / Q000139:chemically induced*; D006801:Humans; D007649:Ketamine / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D009609:Nitrous Oxide / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D000778:Anesthetics, Dissociative; D018757:GABA Modulators; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D009609:Nitrous Oxide