title: N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss.
abstract: The use of aminoglycoside antibiotics is limited by ototoxicity that can produce permanent hearing loss. We report that concurrent administration of N-methyl-D-aspartate (NMDA) antagonists markedly attenuates both the hearing loss and destruction of cochlear hair cells in guinea pigs treated with aminoglycoside antibiotics. These findings indicate that aminoglycoside-induced hearing loss is mediated, in part, through an excitotoxic process. The high correlation (Spearman correlation coefficient: 0.928; P < 0.01) obtained between the relative cochleotoxicities of a series of aminoglycosides in humans and the potencies of these compounds to produce a polyamine-like enhancement of [3H]dizocilpine binding to NMDA receptors is consistent with this hypothesis, and provides a simple in vitro assay that can predict this aspect of aminoglycoside-induced ototoxicity.
authors.affiliation: Laboratory of Neuroscience, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Basile
authors.forename: J M
authors.initials: JM
authors.lastname: Huang
authors.forename: C
authors.initials: C
authors.lastname: Xie
authors.forename: D
authors.initials: D
authors.lastname: Webster
authors.forename: C
authors.initials: C
authors.lastname: Berlin
authors.forename: P
authors.initials: P
authors.lastname: Skolnick
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D003051:Cochlea / Q000473:pathology; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory; D034381:Hearing Loss / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006320:Hearing Tests; D007612:Kanamycin / Q000009:adverse effects; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009355:Neomycin / Q000009:adverse effects; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D016548:Prosencephalon; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D007612:Kanamycin; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D009355:Neomycin; C010739:ifenprodil