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

**Authors:** Yazen Alnefeesi, Ramilya Z. Murtazina, Raul R. Gainetdinov

PMC · DOI: 10.62641/aep.v53i5.1916 · Actas Españolas de Psiquiatría · 2025-10-05

## TL;DR

This paper explores trace amine-associated receptors (TAARs) as potential new targets for treating bipolar disorders.

## Contribution

The paper highlights TAARs as novel therapeutic targets for bipolar disorders based on their role in neurological functions and signaling.

## Key findings

- TAAR1 agonist Ulotaront has advanced to Phase III trials for schizophrenia and is being tested for depression and anxiety.
- TAARs are linked to key neurological functions like plasticity and neurogenesis, relevant to bipolar disorders.
- Available data suggest TAARs could serve as transdiagnostic targets for multiple psychiatric conditions.

## Abstract

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.

## Linked entities

- **Genes:** TAAR1 (trace amine associated receptor 1) [NCBI Gene 134864], TAAR2 (trace amine associated receptor 2) [NCBI Gene 9287], TAAR5 (trace amine associated receptor 5) [NCBI Gene 9038], TAAR6 (trace amine associated receptor 6) [NCBI Gene 319100], TAAR8 (trace amine associated receptor 8) [NCBI Gene 83551], TAAR9 (trace amine associated receptor 9) [NCBI Gene 134860]
- **Chemicals:** Ulotaront (PubChem CID 89532783)
- **Diseases:** schizophrenia (MONDO:0005090), major depressive disorder (MONDO:0002009), generalized anxiety disorder (MONDO:0001942)

## Full-text entities

- **Genes:** TAAR2 (trace amine associated receptor 2) [NCBI Gene 9287] {aka GPR58, taR-2}, TAAR6 (trace amine associated receptor 6) [NCBI Gene 319100] {aka TA4, TAR4, TAR6, TRAR4, taR-4, taR-6}, TAAR9 (trace amine associated receptor 9) [NCBI Gene 134860] {aka TA3, TAR3, TAR9, TRAR3}, TAAR1 (trace amine associated receptor 1) [NCBI Gene 134864] {aka TA1, TAR1, TRAR1}, TAAR8 (trace amine associated receptor 8) [NCBI Gene 83551] {aka GPR102, TA5, TAR5, TRAR5, TaR-5, TaR-8}, TAAR5 (trace amine associated receptor 5) [NCBI Gene 9038] {aka PNR, taR-5}
- **Diseases:** schizophrenia (MESH:D012559), GAD (MESH:C000726808), MDD (MESH:D003865), Bipolar Disorders (MESH:D001714)
- **Chemicals:** Ulotaront (MESH:C000705647), dopamine (MESH:D004298), serotonin (MESH:D012701)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

151 references — full list in the complete paper: https://tomesphere.com/paper/PMC12538607/full.md

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Source: https://tomesphere.com/paper/PMC12538607