Oestreicher E, Arnold W, Ehrenberger K, Felix D
ENT Department, Technical University of Munich, Germany.
ORL J Otorhinolaryngol Relat Spec. 1998 Jan-Feb;60(1):18-21. doi: 10.1159/000027556.
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.
内毛细胞与传入神经元之间的谷氨酸能突触似乎参与了耳蜗的病理生理状况。在噪声创伤和局部缺血期间，内毛细胞中谷氨酸的过度释放会影响传入神经元。耳鸣时，外毛细胞或内毛细胞功能障碍或损伤可能导致内毛细胞谷氨酸自发释放改变。因此，谷氨酸能神经传递的药理学调节在某些内耳疾病的治疗中可能具有重要价值。最近，人们发现解痉药美金刚具有抗谷氨酸能特性。作为一种可能用于治疗内耳疾病的药物，我们对内耳毛细胞神经传递的作用感兴趣。借助微离子电泳技术，我们能够证明美金刚对自发活动以及谷氨酸诱导的活动具有强烈的抑制作用。这种作用似乎是由N-甲基-D-天冬氨酸（NMDA）受体的阻断介导的，因为美金刚对NMDA诱导的活动有强烈的抑制作用，但对AMPA诱导的活动没有抑制作用。这些结果表明美金刚可用于治疗内耳疾病，例如尤其是耳鸣。
