Polyamine-like actions of aminoglycosides and aminoglycoside derivatives at NMDA receptors

European Journal of Pharmacology
J A Segal, P Skolnick

Abstract

Recent pharmacological studies indicate that aminoglycoside-induced hearing loss may be an excitotoxic process modulated by a polyamine-like activation of cochlear NMDA receptors. Aminoglycoside antibiotics are constituted by a series of glycosidically linked aminocyclitols and aminosugars. We report here on the actions of these individual aminocyclitols and aminosugars on wild type NMDA receptors from rat brain. Compared to the parent molecules, neither aminocyclitols (e.g., 2-deoxystreptamine, streptamine, and streptidine) nor aminosugars (e.g., D-glucosamine and kanosamine) were effective at enhancing [3H]dizocilpine ([3H]MK-801) binding or inhibiting [3H]ifenprodil at NMDA receptors. Moreover, the appropriate combinations of aminosugars and aminocyclitols did not reconstitute the activity of the parent aminoglycoside at NMDA receptors. These data indicate that the polyamine-like actions of aminoglycosides are attributable to the conformation of the parent molecule rather than a particular amine containing constituent. Thus, it may be possible to synthesize or isolate aminoglycoside antibiotics devoid of ototoxicity.

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Citations

Dec 28, 2006·Apoptosis : an International Journal on Programmed Cell Death·Eric LecainPatricia Crisanti
Jan 8, 1999·Brain Research·J A SegalP Skolnick
Apr 20, 2000·European Journal of Pharmacology·G Höfner, K T Wanner
Jan 14, 2000·European Journal of Pharmacology·S C HarveyH A Kirst
Dec 18, 2001·Hearing Research·C T TanS Y Lin-Shiau
Jun 10, 2006·BMC Pharmacology·Mark Evan GoldmanTom Humphreys
Aug 11, 2016·Indian Journal of Otolaryngology and Head and Neck Surgery : Official Publication of the Association of Otolaryngologists of India·Miraj AhmedSunil Kumar
Mar 4, 2014·International Journal of Pediatric Otorhinolaryngology·Fadlullah AksoyÖnder Hüseyinbas
Jun 22, 2013·Pediatric Blood & Cancer·Kenneth S ChenNaomi J Winick
Nov 2, 2014·The Annals of Otology, Rhinology, and Laryngology·Fadlullah AksoyBurak Ozturk
Mar 17, 2000·Current Opinion in Neurology·P F Smith

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