TAAR1 Potential for Treatment of Stress Disorders

AI Summary

Stress is a major risk factor for MDD, anxiety, PTSD and bipolar disorder, while existing treatments frequently fail to meet clinical needs.
TAAR1 modulates stress responses across animal models and is implicated in stress-related psychopathologies.
Selective TAAR1 agonists show promising efficacy; mechanisms may involve TAAR1 expression in stress-related brain regions and modulation of dopamine, serotonin and glutamate.

Handb Exp Pharmacol. 2026 Jul 17. doi: 10.1007/164_2026_822. Online ahead of print.

ABSTRACT

Substantial evidence indicates that stress serves as a major risk factor for various psychiatric disorders, including major depressive disorder (MDD), anxiety disorders, post-traumatic stress disorder (PTSD), and bipolar disorder. Although multiple therapeutic options exist for these conditions, current treatments often fall short of meeting clinical needs. Since the identification of trace amine-associated receptor 1 (TAAR1), studies across diverse animal models have revealed its involvement in modulating stress responses and its potential role in stress-related psychopathologies. Several selective TAAR1 agonists have shown promising efficacy in alleviating certain stress-induced adverse effects. While the underlying mechanisms remain incompletely understood, emerging evidence suggests they may involve TAAR1 expression in key brain regions regulating stress, as well as its modulatory effects on neurotransmitter systems – such as dopamine, serotonin, and glutamate. This chapter summarizes current research on TAAR1, with a focus on the role of TAAR1 ligands in stress-related disorders. Additionally, we briefly discuss TAAR1-related signaling pathways in stress regulation and the pharmacology of TAAR1 agonists.

PMID:42463872 | DOI:10.1007/164_2026_822

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