Translocator Protein (18 kD) as Target for Anxiolytics Without Benzodiazepine-Like Side Effects
Translocator Protein (18 kD) as Target for Anxiolytics Without Benzodiazepine-Like Side Effects
复制标题
DOI：
10.1126/science.1175055
复制
发表时间：
2009-07-24
期刊：
影响因子：
56.9
通讯作者：
Kucher, Klaus
中科院分区：
文献类型：
--
作者：
Rupprecht, Rainer;Rammes, Gerhard;Kucher, Klaus
大多数抗焦虑药物（抗焦虑药）通过调节大脑中的神经递质起作用。苯二氮卓类药物是快速有效的抗焦虑药物；然而，它们的长期使用受到耐受性和戒断症状的限制。转运蛋白的配体[18千道尔顿（kD）]可能促进内源性神经类固醇的合成，这在动物模型中也具有抗焦虑作用。在这里，我们发现转运蛋白（18kd）配体XBD173增强了γ -氨基丁酸介导的神经传递，并在没有镇静和耐受性发育的情况下抵消了诱导的恐慌发作。与苯二氮卓类药物相比，XBD173在人体中也具有抗恐慌活性，不会引起镇静或戒断症状。因此，转运蛋白（18kd）配体是有希望的速效抗焦虑药物的候选者，其副作用比苯二氮卓类药物更轻。
Most antianxiety drugs (anxiolytics) work by modulating neurotransmitters in the brain. Benzodiazepines are fast and effective anxiolytic drugs; however, their long-term use is limited by the development of tolerance and withdrawal symptoms. Ligands of the translocator protein [18 kilodaltons (kD)] may promote the synthesis of endogenous neurosteroids, which also exert anxiolytic effects in animal models. Here, we found that the translocator protein (18 kD) ligand XBD173 enhanced gamma-aminobutyric acid-mediated neurotransmission and counteracted induced panic attacks in rodents in the absence of sedation and tolerance development. XBD173 also exerted antipanic activity in humans and, in contrast to benzodiazepines, did not cause sedation or withdrawal symptoms. Thus, translocator protein (18 kD) ligands are promising candidates for fast-acting anxiolytic drugs with less severe side effects than benzodiazepines.