Trace Amine-Associated Receptor 1 (TAAR1): A new drug target for psychiatry?

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 5HT1A 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.