Staecker Hinrich, Maxwell Kenneth S, Morris John R, van de Heyning Paul, Morawski Krzysztof, Reintjes Frank, Meyer Thomas
Department of Otolaryngology, Head and Neck Surgery, University of Kansas Medical Center, Kansas City, Kans., USA.
Audiol Neurootol. 2015;20(3):172-82. doi: 10.1159/000369608. Epub 2015 Apr 8.
Inhibition of cochlear N-methyl-D-aspartate (NMDA) receptors with AM-101, a small molecule antagonist delivered by intratympanic injection, represents a novel approach to treat acute tinnitus triggered by glutamate excitotoxicity. An earlier double-blind, randomized, placebo-controlled phase II clinical trial (TACTT0) had demonstrated a significant and dose-dependent improvement in tinnitus triggered by acute acoustic trauma or otitis media from baseline to day 90. A second phase II trial (TACTT1) now sought to evaluate the most appropriate dose regimen for this treatment. Outcomes from the TACTT1 trial showed no significant difference in tinnitus improvement between a single-dose treatment and a dose regimen comprising three doses over 2 weeks. Taken together, three injections over 3 consecutive days showed the best results in the two phase II trials, suggesting that repeated and concentrated inhibition of cochlear NMDA receptors provides best treatment effects, while keeping the procedural impact on patients short.
通过鼓室内注射小分子拮抗剂AM-101抑制耳蜗N-甲基-D-天冬氨酸（NMDA）受体，是一种治疗由谷氨酸兴奋性毒性引发的急性耳鸣的新方法。早期的一项双盲、随机、安慰剂对照II期临床试验（TACTT0）已证明，由急性声创伤或中耳炎引发的耳鸣，从基线到第90天有显著且剂量依赖性的改善。现在，第二项II期试验（TACTT1）旨在评估这种治疗的最合适给药方案。TACTT1试验的结果显示，单剂量治疗与2周内分三次给药的方案在耳鸣改善方面无显著差异。综合来看，在两项II期试验中，连续3天注射三次显示出最佳效果，这表明对耳蜗NMDA受体进行反复和集中抑制可提供最佳治疗效果，同时使对患者的操作影响保持在较短时间。
