Trace Amine-associated Receptors (TAARs): Candidate Targets in the Treatment of Bipolar Disorders

There is a need for new medications in the treatment of bipolar disorders. One such prospect is the development of ligands for the trace amine-associated receptors (TAARs). There are six functional TAARs in humans (TAAR1, TAAR2, TAAR5, TAAR6, TAAR8 and TAAR9), four of which are expressed at low levels in key areas of the limbic system. Ulotaront is a TAAR1 agonist that has advanced to Phase III with Food and Drug Administration (FDA) breakthrough status in schizophrenia. The drug is now also undergoing clinical development for both major depressive disorder (MDD) and generalized anxiety disorder (GAD). Herein, we review all currently available data that link the TAARs with common abnormalities in bipolar disorders. Some members of the TAAR family regulate fundamental neurological functions such as plasticity, adult neurogenesis, response inhibition, in addition to dopamine and serotonin signaling. This constitutes a theoretical basis for transdiagnostic applications. The evidence particularly favors the TAARs as novel targets in the treatment of bipolar disorders, thus warranting a dedicated effort at drug discovery.