Li Zelong, Wan Luoting, Dong Jing, Li Jinquan, Liu Jianfeng
School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, China.
College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, Hubei, China.
Front Pharmacol. 2025 Apr 25;16:1598048. doi: 10.3389/fphar.2025.1598048. eCollection 2025.
In the metabolic pathways associated with major biogenic amines, such as dopamine, noradrenaline, and serotonin, there exists a group of compounds known as trace amines. These trace amines share structural similarities with the major biogenic amines. Since the discovery of trace amine-associated receptors (TAARs) that are activated by trace amines, numerous studies have suggested that these receptors, particularly the TAAR1 subfamily, play a role in modulating the stress response and are involved in stress-related psychiatric disorders, including depression, bipolar disorder, and anxiety. Research indicates that TAAR1 regulates the release of neurotransmitters like dopamine and serotonin, which may be a potential mechanism underlying the involvement of trace amines and TAAR1 in response to stress. Several selective TAAR1 agonists have been evaluated in various animal models of depression and anxiety, showing that these compounds can be effective in alleviating depressive and anxiety-like behaviors. Additionally, TAAR5 has also been found to have an effect on anxiety; it is proposed that a TAAR5 antagonist might produce anxiolytic effects. Despite our limited understanding of the underlying mechanisms through which TAARs regulates stress-related disorders, current evidence strongly suggests that TAAR ligands could represent novel pharmacotherapy for treating psychiatric disorders such as depression, bipolar disorder, and anxiety disorders like post-traumatic stress disorder (PTSD). This offers hope for more effective and safer treatment options in the field of mental health.
在与多巴胺、去甲肾上腺素和血清素等主要生物胺相关的代谢途径中，存在着一类被称为痕量胺的化合物。这些痕量胺与主要生物胺在结构上有相似之处。自从发现了可被痕量胺激活的痕量胺相关受体（TAARs）以来，大量研究表明，这些受体，特别是TAAR1亚家族，在调节应激反应中发挥作用，并参与包括抑郁症、双相情感障碍和焦虑症在内的与应激相关的精神疾病。研究表明，TAAR1调节多巴胺和血清素等神经递质的释放，这可能是痕量胺和TAAR1参与应激反应的潜在机制。几种选择性TAAR1激动剂已在各种抑郁症和焦虑症动物模型中进行了评估，结果表明这些化合物可有效减轻抑郁和焦虑样行为。此外，还发现TAAR5对焦虑有影响；有人提出TAAR5拮抗剂可能产生抗焦虑作用。尽管我们对TAARs调节应激相关疾病的潜在机制了解有限，但目前的证据强烈表明，TAAR配体可能代表了治疗抑郁症、双相情感障碍和创伤后应激障碍（PTSD）等焦虑症等精神疾病的新型药物疗法。这为心理健康领域提供了更有效、更安全的治疗选择带来了希望。
