[5] TAAR1 is a primarily intracellular amine-activated Gs-coupled and Gq-coupled G 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 monoamine neurons in the central nervous system (CNS).

[6][7][8][9] 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.

[18][6] 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.

[19][23] Further characterization of the functional role of TAAR1 and other receptors from this family was performed by other researchers including Raul Gainetdinov and his colleagues.

TAAR1 and its homologues have ligand pocket vectors that utilize sets of 35 amino acids known to be involved directly in receptor-ligand interaction.

[25] To date, TAAR1 has been identified and cloned in five different mammal genomes: human, mouse, rat, monkey, and chimpanzee.

[6][14] Outside of the human central nervous system, hTAAR1 also occurs as an intracellular receptor and is primarily expressed in the stomach, intestines,[26] duodenum,[26] pancreatic β-cells, and white blood cells.

[29] A method to induce hTAAR1 membrane expression has been used to study its pharmacology via a bioluminescence resonance energy transfer cAMP assay.

[31][33] These and other reported TAAR1 hetero-oligomers include: [note 2] in the TAAR1- D2sh example shows that TAAR1 can be located at cell membranes, and in the case of enterochromaffin cells in the gut epithelium, TAAR1 can be activated by high doses of dietary 'trace' amines, proximal to vesicles packed with catecholamines, impacting the vagal nerve system and CNS.

[35] Some of the human trace amines include tryptamine, phenethylamine (PEA), N-methylphenethylamine, p-tyramine, m-tyramine, N-methyltyramine, p-octopamine, m-octopamine, and synephrine.

The rank order of potency for the primary endogenous ligands at the human TAAR1 is: tyramine > β-phenethylamine > dopamine = octopamine.

[18][65][36][67] Relatedly, it is not entirely clear whether agents like amphetamine and methamphetamine at typical doses produce significant TAAR1 agonism and associated effects in humans.

[36] As examples, most cathinones (β-ketoamphetamines), such as methcathinone, mephedrone, and flephedrone, as well as other amphetamines, including ephedrine, 4-methylamphetamine (4-MA), para-chloroamphetamine (PCA),[53] para-methoxyamphetamine (PMA), 4-methylthioamphetamine (4-MTA), MDEA, MBDB, 5-APDB, and 5-MAPDB, are inactive as human TAAR1 agonists.

[68][36] Many other drugs acting as monoamine releasing agents (MRAs) are also inactive as human TAAR1 agonists, for instance piperazines like benzylpiperazine (BZP), meta-chlorophenylpiperazine (mCPP), and 3-trifluoromethylphenylpiperazine (TFMPP), as well as the alkylamine methylhexanamine (DMAA).

[18][36][72] The negligible TAAR1 agonism with most cathinones might serve to enhance their effects and misuse potential as MRAs compared to their amphetamine counterparts.

[73][74] Selegiline is only a weak agonist of the mouse TAAR1, with dramatically lower potency than amphetamine or methamphetamine, and does not seem to have been assessed at the human TAAR1.

[10] Through direct activation of G protein-coupled inwardly-rectifying potassium channels (GIRKs), TAAR1 can reduce the firing rate of dopamine neurons, in turn preventing a hyper-dopaminergic state.

[11] Medical reviews from February 2015 and 2016 noted that TAAR1-selective ligands have significant therapeutic potential for treating psychostimulant addictions (e.g., cocaine, amphetamine, methamphetamine, etc.).

[7][8] Despite wide distribution outside of the CNS and PNS, TAAR1 does not affect hematological functions and the regulation of thyroid hormones across different stages of ageing.

[96] A large candidate gene association study published in September 2011 found significant differences in TAAR1 allele frequencies between a cohort of fibromyalgia patients and a chronic pain-free control group, suggesting this gene may play an important role in the pathophysiology of the condition; this possibly presents a target for therapeutic intervention.

[97] In preclinical research on rats, TAAR1 activation in pancreatic cells promotes insulin, peptide YY, and GLP-1 secretion;[98][non-primary source needed] therefore, TAAR1 is potentially a biological target for the treatment of obesity and diabetes.

[98][non-primary source needed] Lack of TAAR1 does not significantly affect sexual motivation and routine lipid and metabolic blood biochemical parameters, suggesting that future TAAR1-based therapies should have a favorable safety profile.