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

Seetal Dodd; André F Carvalho; Basant K Puri; Michael Maes; Chiara C Bortolasci; Gerwyn Morris; Michael Berk

doi:10.1016/j.neubiorev.2020.09.028

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

Neurosci Biobehav Rev. 2021 Jan:120:537-541. doi: 10.1016/j.neubiorev.2020.09.028. Epub 2020 Oct 5.

Authors

Seetal Dodd¹, André F Carvalho², Basant K Puri³, Michael Maes⁴, Chiara C Bortolasci⁵, Gerwyn Morris⁴, Michael Berk⁶

Affiliations

¹ 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. Electronic address: seetald@barwonhealth.org.au.
² 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.
³ C.A.R., Cambridge, UK.
⁴ The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
⁵ The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia; Centre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, Victoria, Australia.
⁶ 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.

PMID: 33031817
DOI: 10.1016/j.neubiorev.2020.09.028

Abstract

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_1A 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.

Keywords: SEP-363856; Trace Amine-Associated Receptor; drug target; schizophrenia.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Humans
Pharmaceutical Preparations*
Psychiatry*
Pyrans
Receptors, G-Protein-Coupled

Substances

Pharmaceutical Preparations
Pyrans
Receptors, G-Protein-Coupled
SEP-363856
Trace amine-associated receptor 1