Potential of Ligands for Trace Amine-Associated Receptor 1 (TAAR1) in the Management of Substance Use Disorders

Autor: Jun-Xu Li, Ruyan Wu
Rok vydání: 2021
Předmět:
Zdroj: CNS Drugs
ISSN: 1179-1934
1172-7047
DOI: 10.1007/s40263-021-00871-4
Popis: Trace amines, including β-phenylethylamine (β-PEA), p-tyramine (TYR), tryptamine (TRP) and p-octopamine (OCT), represent a group of amines expressed at low levels in the mammalian brain. Given the close structural similarities to traditional monoamines, the links between trace amines and the monoaminergic system have long been established. Trace amine associated receptor 1 (TAAR1), the most well characterized receptor in the TAARs family, has been shown to be potently activated by trace amines like TYR and PEA. Meanwhile, catecholamine metabolites and amphetamine analogs are also potent agonists of TAAR1, implicating its role in mediating the monoaminergic system and substance use disorders. In the central nervous system, TAAR1 is expressed in brain regions involved in dopaminergic, serotonergic and glutamatergic transmission. Genetic animal models and electrophysiological studies have revealed that TAAR1 is a potent modulator of the monoaminergic system, and TAAR1 agonists may be potential pharmacotherapies for the treatment of substance use disorders. Selective and potent engineered TAAR1 ligands, including full (RO5166017 and RO5256390) and partial (RO5203648, RO5263397 and RO5073012) agonists and the antagonist EPPTB (N-(3-ethoxyphenyl)-4-(1-pyrrolidinyl)-3-(trifluoromethyl)benzamide, RO5212773), serve as invaluable tools for the investigation of TAAR1 functions and display high potential for the development of TAAR1-based pharmacotherapies for the treatment of substance use disorders. Despite a number of advances that have been made, more clinical studies are warranted in order to test the potential and efficacy of TAAR1 ligands in the treatment of psychiatric disorders, especially substance use disorders.
Databáze: OpenAIRE
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