Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Balassa u. 6, Hungary.
CNS Neurosci Ther. 2010 Apr;16(2):63-75. doi: 10.1111/j.1755-5949.2009.00109.x. Epub 2009 Dec 22.
Preclinical studies demonstrated that ocinaplon, a positive allosteric modulator of GABA(A) receptors, possesses anxiolytic-like actions at doses devoid of the side effects typically associated with benzodiazepines. The aim of this study was to evaluate the effects of ocinaplon in a multicenter, double-blind proof-of-concept trial of male and female outpatients who met DSM-IV criteria for GAD with no coexisting depression, and had a baseline score of > or =20 on the Hamilton Scale for Anxiety (HAM-A). Patients with <20% reduction in HAM-A to placebo in a single-blind 7-day run-in period were randomly assigned to treatment with ocinaplon 90 mg t.i.d. (n = 31) or placebo for 28 days (n = 29). Ocinaplon was more effective than placebo in reducing HAM-A scores (P= 0.009). Patients assigned to ocinaplon exhibited a mean improvement of 14.2 points (SE = 2.6) on the total score of the HAM-A scale at the conclusion of the trial, while patients assigned to placebo obtained a mean improvement of 6.3 points (SE = 2.0). A significant (P= 0.023) difference in improvement between ocinaplon and placebo was observed beginning at and continuing from 1-week after the initiation of dosing. The proportion of patients with treatment-emergent adverse events (TEAE) was not statistically significant between ocinaplon and placebo. One serious adverse event (SAE) occurred in the ocinaplon group that was considered possibly related to study medication (icterus following transaminase elevations). The patient had preexisting medical conditions that may have contributed to this SAE. A full recovery was observed with no residual effects. The overall safety profile revealed no patterns of TEAEs, including those effects typically associated with other anxiolytic and/or benzodiazepine compounds, such as sedation. Ocinaplon appears to be a well-tolerated and effective treatment for GAD. It produces a rapid onset of anxiolytic action absent the side effects (e.g., dizziness, sedation) typically reported following anxiolytic doses of benzodiazepines.
临床前研究表明，奥昔拉隆是一种 GABA(A) 受体的正变构调节剂，在没有通常与苯二氮䓬类药物相关的副作用的剂量下具有抗焦虑作用。本研究的目的是评估奥昔拉隆在一项多中心、双盲概念验证试验中的效果，该试验纳入了符合 DSM-IV 广泛性焦虑症标准的男性和女性门诊患者，这些患者无并发抑郁症，汉密尔顿焦虑量表（HAM-A）基线评分 > 或 =20。在为期 7 天的单盲导入期内，安慰剂治疗后 HAM-A 评分降低<20%的患者被随机分配接受奥昔拉隆 90 mg，每日 3 次（n = 31）或安慰剂治疗 28 天（n = 29）。奥昔拉隆在降低 HAM-A 评分方面比安慰剂更有效（P = 0.009）。接受奥昔拉隆治疗的患者在试验结束时 HAM-A 总分平均改善 14.2 分（SE = 2.6），而接受安慰剂治疗的患者平均改善 6.3 分（SE = 2.0）。从开始给药后 1 周开始并持续观察到奥昔拉隆与安慰剂之间的改善有显著差异（P = 0.023）。奥昔拉隆和安慰剂组患者出现治疗中出现的不良事件（TEAE）的比例无统计学意义。奥昔拉隆组发生 1 例严重不良事件（SAE），认为可能与研究药物有关（转氨酶升高后出现黄疸）。该患者有潜在的医疗条件，可能导致该 SAE。完全康复，无残留影响。总体安全性概况未显示出 TEAEs 的模式，包括那些与其他抗焦虑和/或苯二氮䓬类化合物通常相关的效应，如镇静。奥昔拉隆似乎是一种耐受性良好且有效的广泛性焦虑症治疗药物。它能迅速产生抗焦虑作用，而没有通常在抗焦虑剂量的苯二氮䓬类药物后报告的副作用（例如头晕、镇静）。
