Yamauchi Miki, Hiraoka Shuichi, Imanishi Taiichiro
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, 222-8567 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2006 Nov;26(5-6):193-8.
Some selective serotonin reuptake inhibitors (SSRIs) have recently been approved for the treatment of anxiety disorders such as obsessive-compulsive disorder, panic disorder and social anxiety disorder, and they are considered first-line treatment for anxiety disorders in Japan as well as in other countries. Previous clinical studies have suggested that the 5-HT2C receptors in subjects with anxiety disorders are hypersensitive. We recently reported that chronic treatment with fluvoxamine or paroxetine desensitized 5-HT2C receptor function. The desensitization of 5-H T2C receptor function has also been reported with other SSRIs and is considered to be a common mechanism of action of SSRIs in the treatment of anxiety disorders. In addition, some studies have suggested that 5-HT2A receptors and 5-HTIA receptors participate in anxiety disorders and the therapeutic mechanism. Both clinical studies and animal studies have indicated that the amygdala plays an essential role in anxiety and fear response. Thus, it may be important to elucidate functional changes in these 5-HT receptor subtypes in brain regions including the amygdala under the chronic administration of SSRIs to understand the anxiolytic mechanism of SSRIs.
一些选择性5-羟色胺再摄取抑制剂（SSRI）最近已被批准用于治疗焦虑症，如强迫症、恐慌症和社交焦虑症，在日本以及其他国家它们都被视为焦虑症的一线治疗药物。以往的临床研究表明，焦虑症患者体内的5-HT2C受体高度敏感。我们最近报告称，长期使用氟伏沙明或帕罗西汀会使5-HT2C受体功能脱敏。其他SSRI也有5-HT2C受体功能脱敏的报告，这被认为是SSRI治疗焦虑症的一种常见作用机制。此外，一些研究表明，5-HT2A受体和5-HT1A受体也参与了焦虑症及其治疗机制。临床研究和动物研究均表明，杏仁核在焦虑和恐惧反应中起着至关重要的作用。因此，阐明在长期服用SSRI的情况下，包括杏仁核在内的脑区中这些5-HT受体亚型的功能变化，对于理解SSRI的抗焦虑机制可能很重要。
