POLYAMINE-LIKE ACTIONS OF AMINOGLYCOSIDES AND AMINOGLYCOSIDE DERIVATIVES AT NMDA RECEPTORS

Recent pharmacological studies indicate that aminoglycoside-induced he aring 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 a minosugars. We report here on the actions of these individual aminocyc litols and aminosugars on wild type NMDA receptors from rat brain. Com pared to the parent molecules, neither aminocyclitols (e.g., 2-deoxyst reptamine, streptamine, and streptidine) nor aminosugars (e.g., D-gluc osamine and kanosamine) were effective at enhancing [H-3]dizocilpine ( [H-3]MK-801) binding or inhibiting [3H]ifenprodil at NMDA receptors. M oreover, the appropriate combinations of aminosugars and aminocyclitol s did not reconstitute the activity of the parent aminoglycoside at NM DA receptors. These data indicate that the polyamine-like actions of a minoglycosides are attributable to the conformation of the parent mole cule rather than a particular amine containing constituent. Thus, it m ay be possible to synthesize or isolate aminoglycoside antibiotics dev oid of ototoxicity. Published by Elsevier Science B.V.