Memantine suppresses the glutamatergic neurotransmission of mammalian inner hair cells.
The glutamatergic synapses between inner hair cells and afferent neurons seem to be involved in pathophysiological conditions of the cochlea. The excessive release of glutamate from inner hair cells during noise trauma and ischemia affects the afferent neurons. It is possible that in tinnitus outer hair cell or inner hair cell dysfunction or damage leads to an altered spontaneous release of glutamate from inner hair cells. Thus, the pharmacological modulation of glutamatergic neurotransmission could be of great value in the therapy of certain inner ear diseases. Recently, it has been discovered that the spasmolytic drug memantine has antiglutamatergic properties. As a possible drug for inner ear diseases, we were interested in the action of memantine on the neurotransmission of inner hair cells. With the aid of microiontophoretic techniques we were able to show a strong depressing effect on spontaneous activity as well as on glutamate-induced activity. This effect seems to be mediated by a blockade of N-methyl-D-aspartate (NMDA) receptors as memantine showed a strong inhibiting effect on NMDA-induced activity but not on AMPA-induced activity. These results recommend memantine for the treatment of inner ear diseases, e.g. especially tinnitus.
Oestreicher
E
E
ENT Department, Technical University of Munich, Germany. e.oestreicher@lrz.tu-muenchen.de
Arnold
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W
Ehrenberger
K
K
Felix
D
D
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects*; D008559:Memantine / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008559:Memantine