[Ototoxic mechanism of aminoglycoside antibiotics--role of glutaminergic NMDA receptors]

Abstract

Recent studies have indicated that glutamatergic NMDA receptors in the cochlea may be involved in ototoxic effects of aminoglycosides in animal subjects. Aminoglycoside antibiotics enhance the function of NMDA receptors by interaction with a polyamine modulatory site. Accordingly, high doses of aminoglycosides may increase calcium entry through the NMDA receptor-associated channel and promote degeneration of hair cells and cochlear nerve fibers. In line with the above, a polyamine site antagonist, ifenprodil as well as a high-affinity channel blocker, dizocilpine (MK-801) attenuates ototoxic effects of aminoglycosides in rats. Notably, ifenprodil as well as low-affinity channel blockers (e.g. memantine and amantadine) may be safely used in humans. Taken together, the above findings seem to open new avenues of research on selective pharmacotherapy of aminoglycosides-induced ototoxicity in humans.