title: Effect of ketamine, dextromethorphan, and MK-801 on cochlear dysfunction induced by transient ischemia.
abstract: Overstimulation of the N-methyl-D-aspartate (NMDA) glutamate receptor has been implicated as a factor in the pathogenesis of hypoxic-ischemic injury in the central nervous system. To evaluate the role played by NMDA antagonists in ischemia-reperfusion injury of the cochlea, 3 noncompetitive NMDA antagonists--ketamine, dextromethorphan, and MK-801--were administered to 53 albino guinea pigs subjected to transient ischemia of 30 minutes' duration, and the threshold shifts of the compound action potential were compared with those of nontreated animals 4 hours after the onset of recirculation. Ketamine and dextromethorphan moderately ameliorated the compound action potential threshold shifts, whereas MK-801, the most potent NMDA receptor antagonist among these 3 agents, did not show any protective effect. These results indicate that the action antagonizing the NMDA receptor has no protective effect against ischemia-reperfusion injury of the cochlea, and that ketamine and dextromethorphan act as protective agents for the cochlea via other pathways.
authors.affiliation: Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tabuchi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tsuji
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Wada
authors.forename: Zenya
authors.initials: Z
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Jun
authors.initials: J
authors.lastname: Kusakari
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003051:Cochlea / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D003915:Dextromethorphan / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006168:Guinea Pigs; D007649:Ketamine / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D003915:Dextromethorphan