An Experimental Study on the Protective Effect of Memantine in Noise‐Induced Hearing Loss

ABSTRACT Objective This study examined the potential protective effects of memantine, an N‐methyl‐D‐aspartate (NMDA) receptor antagonist, against acoustic trauma (AT) in guinea pigs, using electrophysiological and histopathological analyses. Methods Thirty guinea pigs with normal hearing were divided into six groups ( n = 5 per group): Group 1 (control), Group 2 (AT, early), Group 3 (AT, late), Group 4 (AT + steroid), Group 5 (AT + saline), and Group 6 (AT + memantine). AT was induced using 6–10 kHz broadband noise at 115–120 dB for 1.5–2.0 h. Animals received intraperitoneal injections of memantine, steroid, or saline 1.5 h before AT. Measurements were obtained at baseline, 2 h, 7 days, 14 days, and 21 days post‐AT. Distortion product otoacoustic emissions (DPOAE) signal‐to‐noise ratios (SNRs) were measured from 1 to 32 kHz, and auditory brainstem response (ABR) from 8 to 32 kHz. Group 2 animals were euthanized within 2 h after AT; others after the 21‐day evaluation. Cochlear histopathology was evaluated postmortem. Results Baseline ABR thresholds were < 30 dB SPL, and DPOAE SNRs were ≥ 6 dB. Group 6 showed improved DPOAE SNRs at 1.5 and 24 kHz compared to Groups 3 and 5. ABR thresholds in Group 6 were lower than those in Group 3 (16, 24 kHz) and Group 5 (32 kHz). Group 4 showed lower thresholds than Group 3 at 12–24 kHz. Histology revealed milder cochlear damage in Group 6 compared to Groups 2, 3, and 5. Conclusion Memantine demonstrated protective effects against noise‐induced hearing loss. Further studies are needed to clarify its molecular mechanisms.