Effect of Ketamine, Dextromethorphan, and MK-801 on Cochlear Dysfunction Induced by Transient Ischemia

• Published in: Annals of otology, rhinology & laryngology Vol. 111; no. 1; pp. 44 - 49
• Main Authors: Tabuchi, Keiji, Ito, Zenya, Tsuji, Shigeki, Hara, Akira, Wada, Tetsuro, Kusakari, Jun
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2002; Annals Publishing Compagny; SAGE PUBLICATIONS, INC
• Subjects: Action Potentials - drug effects; Animals; Biological and medical sciences; Cochlea - blood supply; Cochlea - drug effects; Cochlea - physiopathology; Dextromethorphan - pharmacology; Dizocilpine Maleate - pharmacology; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Ent. Stomatology; Guinea Pigs; Ketamine - pharmacology; Medical sciences; Non tumoral diseases; Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - physiology; Reperfusion Injury - physiopathology; cochlea; compound action potential; noncompetitive NMDA antagonist; ischemia; Morphinan derivatives; Intraperitoneal administration; Intravenous administration; Cardiovascular disease; Opiates; Dextromethorphan; Ischemia; ENT disease; Biological effect; Ungulata; Induction; Internal ear disease; Antitussive agent; Experimental study; Transitory; Pig; Vertebrata; Chemotherapy; Mammalia; Ketamine; Treatment; General anesthetic; Animal; Cochlea; Artiodactyla
• ISSN: 0003-4894; 1943-572X
• DOI: 10.1177/000348940211100107

Overstimulation of the A'-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.