Topic summary
TAAR1
Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the TAAR1gene.
TAAR1 is a primarily intracellularamine-activated Gs-coupled and Gq-coupledG protein-coupled receptor (GPCR) that is primarily expressed in several peripheral organs and cells (e.g., the stomach, small intestine, duodenum, and white blood cells), astrocytes, and in the intracellular milieu within the presynaptic plasma membrane (i.e., axon terminal) of monoamineneurons in the central nervous system (CNS).
TAAR1 is one of six functional human TAARs, which are so named for their ability to bind endogenous amines that occur in tissues at trace concentrations. TAAR1 plays a significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS; it also affects immune system and neuroimmune system function through different mechanisms.
Endogenous ligands of the TAAR1 include trace amines, monoamine neurotransmitters, and certain thyronamines. The trace amines β-phenethylamine, tyramine, tryptamine, and octopamine, the monoamine neurotransmitters dopamine and serotonin, and the thyronamine 3-iodothyronamine (3-IT) are all agonists of the TAAR1 in different species. Other endogenous agonists are also known. A variety of exogenouscompounds and drugs are TAAR1 agonists as well, including various phenethylamines, amphetamines, tryptamines, and ergolines, among others. There are marked species differences in the interactions of ligands with the TAAR1, resulting in greatly differing affinities, potencies, and efficacies of TAAR1 ligands between species. Many compounds that are TAAR1 agonists in rodents are much less potent or inactive at the TAAR1 in humans.
A number of selective TAAR1 ligands have been developed, for instance the TAAR1 full agonistRO5256390, the TAAR1 partial agonistRO5263397, and the TAAR1 antagonistsEPPTB and RTI-7470-44. Selective TAAR1 agonists are used in scientific research, and a few TAAR1 agonists, such as ulotaront and ralmitaront, are being developed as novel pharmaceutical drugs, for instance to treat schizophrenia and substance use disorder.