title: NMDA antagonist neurotoxicity: mechanism and prevention.
abstract: Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, including phencyclidine (PCP) and ketamine, protect against brain damage in neurological disorders such as stroke. However, these agents have psychotomimetic properties in humans and morphologically damage neurons in the cerebral cortex of rats. It is now shown that the morphological damage can be prevented by certain anticholinergic drugs or by diazepam and barbiturates, which act at the gamma-aminobutyric acid (GABA) receptor-channel complex and are known to suppress the psychotomimetic symptoms caused by ketamine. Thus, it may be possible to prevent the unwanted side effects of NMDA antagonists, thereby enhancing their utility as neuroprotective drugs.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: J W
authors.initials: JW
authors.lastname: Olney
authors.forename: J
authors.initials: J
authors.lastname: Labruyere
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: D F
authors.initials: DF
authors.lastname: Wozniak
authors.forename: M T
authors.initials: MT
authors.lastname: Price
authors.forename: M A
authors.initials: MA
authors.lastname: Sesma
mesh_terms: D000818:Animals; D001463:Barbiturates / Q000494:pharmacology; D002642:Chick Embryo; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors*; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D010276:Parasympatholytics / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology; D014617:Vacuoles / Q000648:ultrastructure
chemical_list: D001463:Barbiturates; D009498:Neurotoxins; D010276:Parasympatholytics; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine; D016291:Dizocilpine Maleate; D012601:Scopolamine