Dodd Seetal, F Carvalho André, Puri Basant K, Maes Michael, Bortolasci Chiara C, Morris Gerwyn, Berk Michael
The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia; Centre for Youth Mental Health, University of Melbourne, Parkville, Australia; Department of Psychiatry, University of Melbourne, Parkville, Australia; University Hospital Geelong, Barwon Health, PO Box 281, Geelong, Victoria, 3220, Australia.
The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia; Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Department of Psychiatry, Toronto, ON, Canada.
Neurosci Biobehav Rev. 2021 Jan;120:537-541. doi: 10.1016/j.neubiorev.2020.09.028. Epub 2020 Oct 5.
There are nine subfamilies of TAARs. They are predominantly intracellular, located in the central nervous system and peripherally. They have a role in homeostasis and rheostasis, and also in olfaction. They demonstrate significant cross-talk with the monoamine system and are involved in the regulation of cAMP signalling and K channels. There is evidence to suggest that TAAR1 may be a promising therapeutic target for the treatment of schizophrenia, psychosis in Parkinson's disease, substance use disorders, and the metabolic syndrome and obesity. TAAR1 expression may also be a prognostic biomarker for cancers. A number of TAAR modulators have been identified, including endogenous ligands and new chemical entities. Some of these agents have shown efficacy in animal models of addiction behaviours, depression and anxiety. Only one agent, SEP-363856, has progressed to randomised clinical trials in humans; however further, larger studies with SEP-363856 are required to clarify its suitability as a new treatment for schizophrenia spectrum disorders. SEP-363856 is an agonist of TAAR1 and 5HT and it is not clear to what extent its efficacy can be attributed to TAAR1 rather than to other drug targets. However, current research suggests that TAAR1 has an important role in human physiology and pathophysiology. TAAR1 modulators may become an important new drug class for the management of a wide array of mental disorders in the future.
痕量胺相关受体（TAARs）有九个亚家族。它们主要位于细胞内，分布于中枢神经系统和外周。它们在体内平衡和稳态调节中发挥作用，也参与嗅觉过程。它们与单胺系统存在显著的相互作用，参与环磷酸腺苷（cAMP）信号传导和钾通道的调节。有证据表明，TAAR1可能是治疗精神分裂症、帕金森病中的精神病、物质使用障碍以及代谢综合征和肥胖症的一个有前景的治疗靶点。TAAR1表达也可能是癌症的一种预后生物标志物。已经鉴定出多种TAAR调节剂，包括内源性配体和新型化学实体。其中一些药物在成瘾行为、抑郁和焦虑的动物模型中显示出疗效。只有一种药物SEP - 363856已进入人体随机临床试验；然而，需要对SEP - 363856进行进一步的、更大规模的研究，以明确其作为精神分裂症谱系障碍新治疗方法的适用性。SEP - 363856是TAAR1和5 - 羟色胺（5HT）的激动剂，目前尚不清楚其疗效在多大程度上可归因于TAAR1而非其他药物靶点。然而，目前的研究表明TAAR1在人类生理和病理生理过程中具有重要作用。未来，TAAR1调节剂可能成为治疗多种精神障碍的一类重要新药。
