TAAR1 as an emerging target for the treatment of psychiatric disorders.

Pharmacol Ther

Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York, 955 Main Street, Buffalo, NY 14203, USA. Electronic address:

Published: January 2024

Trace amines, a group of amines expressed at the nanomolar level in the mammalian brain, can modulate monoamine transmission. The discovery of and the functional research on the trace amine-associated receptors (TAARs), especially the most well-characterized TAAR1, have largely facilitated our understanding of the function of the trace amine system in the brain. TAAR1 is expressed in the mammalian brain at a low level and widely distributed in the monoaminergic system, including the ventral tegmental area and substantial nigra, where the dopamine neurons reside in the mammalian brain. Growing in vitro and in vivo evidence has demonstrated that TAAR1 could negatively modulate monoamine transmission and play a crucial role in many psychiatric disorders, including schizophrenia, substance use disorders, sleep disorders, depression, and anxiety. Notably, in the last two decades, many studies have repeatedly confirmed the pharmacological effects of the selective TAAR1 ligands in various preclinical models of psychiatric disorders. Recent clinical trials of the dual TAAR1 and serotonin receptor agonist ulotaront also revealed a potential efficacy for treating schizophrenia. Here, we review the current understanding of the TAAR1 system and the recent advances in the elucidation of behavioral and physiological properties of TAAR1 agonists evaluated both in preclinical animal models and clinical trials. We also discuss the potential TAAR1-dependent signaling pathways and the cellular mechanisms underlying the inhibitory effects of TAAR1 activation on drug addiction. We conclude that TAAR1 is an emerging target for the treatment of psychiatric disorders.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pharmthera.2023.108580DOI Listing

Publication Analysis

Top Keywords

psychiatric disorders
16
mammalian brain
12
taar1
10
taar1 emerging
8
emerging target
8
target treatment
8
treatment psychiatric
8
modulate monoamine
8
monoamine transmission
8
clinical trials
8

Similar Publications

Discriminative stimulus properties of α-ethyltryptamine (α-ET) in rats: α-ET-like effects of MDMA, MDA and aryl-monomethoxy substituted derivatives of α-ET.

Psychopharmacology (Berl)

December 2024

Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, 800 E. Leigh St., STE 205, Richmond, VA, 23219-0540, USA.

Rationale α-ET (α-ethyltryptamine), a homolog of the classical hallucinogen α-methyltryptamine, was once prescribed clinically as an antidepressant. Classical psychedelic drugs are currently of interest as potential pharmacotherapy for psychiatric disorders. Objectives Drug discrimination was used to (a) determine if α-ET-like stimulus effects could be engendered by the prototypical phenylalkylamines MDMA ("Ecstasy") or MDA ("Love Drug") and (b) evaluate the α-ET-like stimulus effects of four synthesized aryl-substituted monomethoxy analogs of α-ET (4-OMe-, 5-OMe-, 6-OMe- and 7-OMe-α-ET).

View Article and Find Full Text PDF

Objective: Disordered Eating Behaviors (DEB) are associated with dysfunctional changes in eating behavior, not meeting diagnostic criteria for eating disorders. DEB affects a significant percentage of individuals, yet it remains under-researched. The current study investigates the developmental trajectory and psychopathological correlates of DEB in children and adolescents in Brazil.

View Article and Find Full Text PDF

Background: Existing research has shown that those ageing with severe mental illness face significant challenges in daily life. Attendance at community-based day centres (DCs) is offered to support daily structure and break isolation. However, little is known about the experiences of those receiving this type of support while transitioning into retirement age.

View Article and Find Full Text PDF

Extending Fundamental Cause Theory to Holistic Health.

Sociol Health Illn

January 2025

Center for Public Policy and Health, Kent State University, Kent, Ohio, USA.

Fundamental Cause Theory (FCT) offers a unique middle range and longitudinal understanding of the lasting social causational relationships between certain social conditions and disease/death. In this research note, I argue that FCT should extend its outcome measures beyond physical disease and death into holistic health. I briefly review how FCT is evaluated, explore the proposed extension and discuss some operational and conceptual challenges using mental illness and positive mental health outcomes as exemplars.

View Article and Find Full Text PDF

Background: Substance use disorders are multifaceted conditions influenced by both genetic and environmental factors. Serotonergic pathways are known to be involved in substance use disorder susceptibility, with genetic markers within serotonin receptor genes identified as potential risk factors.

Methods: To further explore this relationship, we conducted a study to investigate the association between several polymorphisms in five serotonin receptor genes (, , ) and substance use disorders (SUD) in Jordanian males by sequencing genotypes in 496 SUD patients and 496 healthy controls.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!