中国科学技术大学最新Cell论文：快速起效、更安全的抗抑郁药物

Core Viewpoint - The article discusses the rising prevalence of depression and introduces a new rapid antidepressant strategy based on selective activation of the 5-HT 1A receptor, which addresses the slow onset of traditional SSRIs [3][6][12]. Group 1: Background on Depression and SSRIs - Depression has become a leading cause of disability globally, surpassing cardiovascular diseases and cancer [3]. - The monoamine hypothesis, proposed in the 1950s, links depression to a deficiency of monoamine neurotransmitters, leading to the development of various antidepressants [3]. - SSRIs are the latest generation of antidepressants that increase serotonin levels in the brain but often take weeks to show effects and can have side effects [3][6]. Group 2: New Research Findings - A research team published a study in the journal Cell, proposing a pathway-selective 5-HT 1A receptor agonist as a rapid antidepressant strategy [5]. - The study introduces TMU4142, a candidate agonist that shows significant rapid antidepressant effects in mouse models [6][8]. - The research characterizes the G i/o signaling features of the 5-HT 1A receptor and identifies the structural interactions with various agonists and G i/o family proteins [8][10]. Group 3: Mechanism and Implications - TMU4142 selectively activates G oA while minimizing G i3 activation, leading to rapid antidepressant effects without activating the 5-HT 1A receptor in the dorsal raphe nucleus [10][12]. - The findings suggest that distinguishing between downstream G i/o signaling pathways of heteroreceptors and autoreceptors could be a promising strategy for developing fast-acting antidepressants [12].