Abstract
Tinnitus, a common otological symptom, lacks clinically approved pharmacological treatments, highlighting an urgent unmet need. This review explores the potential role of NMDARs, key glutamate receptors in the auditory system, in tinnitus pathophysiology, including excitotoxicity, synaptic plasticity, and neuropathic pain. Alterations in NMDAR variants with different subunit compositions during development have also been implicated in the onset of tinnitus. Clinical trials of NMDAR antagonists, such as acamprosate, caroverine, neramexane, and AM-101, have shown promising results, though none are yet approved. These findings highlight the need for further research on NMDARs to advance the development of next-generation targeted pharmacological therapies for tinnitus.