Trace Amine-Associated Receptor 1: A Multimodal Therapeutic Target for Neuropsychiatric Diseases

Expert Opin Ther Targets. 2018 Jun;22(6):513-526. doi: 10.1080/14728222.2018.1480723. Epub 2018 Jun 5.

Abstract

The trace amines, endogenous amines closely related to the biogenic amine neurotransmitters, have been known to exert physiological and neurological effects for decades. The recent identification of a trace amine-sensitive G protein-coupled receptor, trace amine-associated receptor 1 (TAAR1), and subsequent development of TAAR1-selective small-molecule ligands, has renewed research into the therapeutic possibilities of trace amine signaling. Areas covered: Recent efforts in elucidating the neuropharmacology of TAAR1, particularly in neuropsychiatric and neurodegenerative disease, addiction, and regulation of arousal state, will be discussed. Focused application of TAAR1 mutants, synthetic TAAR1 ligands, and endogenous biomolecules such as 3-iodothyronamine (T1AM) has yielded a basic functional portrait for TAAR1, despite a complex biochemistry and pharmacology. The close functional relationship between TAAR1 and dopaminergic signaling is likely to underlie many of its CNS effects. However, TAAR1's influences on serotonin and glutamate neurotransmission will also be highlighted. Expert opinion: TAAR1 holds great promise as a therapeutic target for mental illness, addiction, and sleep disorders. A combination of preclinical and translationally driven studies has solidified TAAR1 as a key node in the regulation of dopaminergic signaling. Continued focus on the mechanisms underlying TAAR1's regulation of serotonin and glutamate signaling, as well as dopamine, will yield further disease-relevant insights.

Keywords: Dopamine; addiction; depression; neuropharmacology; psychostimulants; schizophrenia; serotonin; sleep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dopamine / metabolism
  • Drug Design
  • Humans
  • Ligands
  • Mental Disorders / drug therapy*
  • Mental Disorders / physiopathology
  • Molecular Targeted Therapy*
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction
  • Sleep Wake Disorders / drug therapy
  • Sleep Wake Disorders / physiopathology
  • Substance-Related Disorders / drug therapy
  • Substance-Related Disorders / physiopathology
  • Thyronines / metabolism

Substances

  • 3-iodothyronamine
  • Ligands
  • Receptors, G-Protein-Coupled
  • Thyronines
  • Dopamine
  • Trace amine-associated receptor 1