Title:The Role of Trace Amine-Associated Receptor 1 (TAAR1) in the Pathophysiology and Treatment of Depression
Volume: 24
Issue: 3
Author(s): Wei Guan*
Affiliation:
- Department of Pharmacology, Pharmacy College, Nantong University, Nantong, 226001, Jiangsu, China
Keywords:
Depression, TAAR1, antidepressant, ulotaront, neuropsychiatric disorders, signalling pathway.
Abstract: Depression is a chronic and recurrent psychiatric condition believed to result from an interaction
between genetic susceptibility and environmental stimuli. Although current therapies prescribed
for depression can be effective, it will take several weeks to demonstrate their full effectiveness
and is often accompanied by side effects and withdrawal symptoms. In this regard, the discovery
of new antidepressant drugs with unique, higher curative effects and fewer adverse reactions is
the pursuit of pharmaceuticals. Trace amine-associated receptor 1 (TAAR1), a G-protein coupled receptor
(GPCR) that is broadly expressed in the mammalian brain, especially within cortical, limbic,
and midbrain monoaminergic regions and activated by “trace amines” (TAs). It is allegedly involved
in modulating dopaminergic, serotonergic, and glutamatergic transmission, which makes TAAR1 a
new drug target for the treatment of dysfunction of monoamine-related disorders. Moreover, TAAR1
agonists have attracted interest as potential treatments for depression due to their role in regulating
monoamine neurotransmission. In fact, Ulotaront (a TAAR1 agonist) is reported to be currently undergoing
phase 2/3 clinical trials in order to test its safety and efficacy in the treatment of major depressive
disorder (MDD). However, the final results of this Phase 2/3 clinical study have not been
announced yet, and the efficacy and safety of Ulotaront in the treatment of depression still need further
observation and research. Thus, this article aims to review evidence of the potential role of
TAAR1 in the pathophysiology and treatment of depression. Moreover, we briefly summarize the
recent findings in the elucidation of behavioral and physiological properties of TAAR1 agonists both
in clinical trials and preclinical animal studies. Collectively, these studies will provide a solid foundation
for TAAR1 as a novel therapeutic target for depression.
