release and reuptake inhibition in different types of monoamine neurons. E.g., a TAAR1 ligand which can easily pass through the norepinephrine transporter, but not the serotonin transporter, will produce – all else equal – markedly greater TAAR1-induced effects in norepinephrine neurons as compared to serotonin neurons. Receptor oligomers TAAR1 forms GPCR oligomers with monoamine autoreceptors in neurons in vivo. These and other reported TAAR1 hetero-oligomers include: TAAR1–D2sh TAAR1–α2A TAAR1–TAAR2 Ligands Agonists Trace amines Trace amines are endogenous amines which act as agonists at TAAR1 and are present in extracellular concentrations of 0.1–10 in the brain, constituting less than 1% of total biogenic amines in the mammalian nervous system. Some of the human trace amines include tryptamine, phenethylamine (PEA), , , , , , , and synephrine. These share structural similarities with the three common monoamines: serotonin, dopamine, and norepinephrine. Each ligand has a different potency, measured as increased cyclic AMP (cAMP) concentration after the binding event. The rank order of potency for the primary endogenous ligands at is:tyramine > β-phenethylamine > dopamine = octopamine. Thyronamines Thyronamines are molecular derivatives of the thyroid hormone and are very important for endocrine system function. 3-Iodothyronamine (T1AM) is the most potent TAAR1 agonist yet discovered, although it lacks monoamine transporter affinity and therefore has little effect in monoamine neurons of the central nervous system. Activation of TAAR1 by T1AM results in the production of large amounts of cAMP. This effect is coupled with decreased body temperature and cardiac output. Synthetic Amphetamine and its substituted derivatives methamphetamine and MDMA are all potent hTAAR1 agonists. Upon association with TAAR1, they elicit increases in cAMP production similar to those of PEA and p-tyramine. These compounds are structurally similar to PEA and p-tyramine. Benzofurans: 5-APB, 5-APDB, 6-APB, 6-APDB, 4-APB, 7-APB, 5-EAPB, and 5-MAPDB, as well as the benzodifuran 2C-B-FLY, are agonists that have an MDMA-like pharmacodynamic profile. The methylphenethylamines are agonists of ; these include α-methylphenethylamine (amphetamine), β-methylphenethylamine, N-methylphenethylamine (a trace amine), 2-methylphenethylamine, 3-methylphenethylamine, and 4-methylphenethylamine. In rats, lysergic acid diethylamide (LSD) is an agonist of , but in humans it lacks any affinity for . Certain 2-aminooxazoline compounds (RO5166017, RO5256390, RO5203648, and RO5263397) are orally bioavailable, highly potent, and selective agonists of TAAR1 in laboratory animals. RO5166017 or (S)-4-[(ethylphenylamino)methyl]-4,5-dihydrooxazol-2-ylamine is a selective TAAR1 agonist without significant activity at other targets. RO5203648 and RO5263397 are highly selective TAAR1 partial agonists. RO5203648 demonstrated clear antidepressant and anti-psychotic activity, additionally