Trace amine-associated receptors were discovered from a search for novel 5-HT receptors [1], where 15 mammalian orthologues were identified and divided into two families. The TA₁ receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee for the Trace amine receptor [4]) has affinity for the endogenous trace amines tyramine, β-phenylethylamine and octopamine in addition to the classical amine dopamine [1]. Emerging evidence suggests that TA₁ is a modulator of monoaminergic activity in the brain [8] with TA₁ and dopamine D₂ receptors shown to form constitutive heterodimers when co-expressed [3]. In addition to trace amines, receptors can be activated by amphetamine-like psychostimulants, and endogenous thyronamines.

In addition to TA₁, in man there are up to 5 functional TAAR genes (TAAR2,5,6,8,9). See [1] for detailed discussion. The product of the gene TAAR2 (also known as GPR58) appears to respond to β-phenylethylamine > tyramine and to couple through G_s [1].

TAAR3, in some individuals, and TAAR4 are pseudogenes in man, although functional in rodents. The signalling characteristics and pharmacology of TAAR₅ (PNR, Putative Neurotransmitter Receptor: TAAR5, O14804), TAAR₆ (Trace amine receptor 4, TaR-4: TAAR6, 96RI8), TAAR₈ (Trace amine receptor 5, GPR102: TAAR8, Q969N4 ) and TAAR₉ (trace amine associated receptor 9: TAAR9, 96RI9) are lacking. The thyronamines, endogenous derivatives of thyroid hormone, have affinity for rodent cloned trace amine receptors, including TA₁ [6]. An antagonist EPPTB has recently been described with a pK_i of 9.1 at the mouse TA₁ but >5.3 for human TA₁ [7].

* Key recommended reading is highlighted with an asterisk

* Maguire JJ, Parker WA, Foord SM, Bonner TI, Neubig RR, Davenport AP. (2009) International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature. Pharmacol Rev, 61 (1): 1-8. [PMID:19325074]

* Pei Y, Asif-Malik A, Canales JJ. (2016) Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications. Front Neurosci, 10: 148. [PMID:27092049]

1. Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S et al.. (2001) Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci USA, 98 (16): 8966-71. [PMID:11459929]

2. Bradaia A, Trube G, Stalder H, Norcross RD, Ozmen L, Wettstein JG, Pinard A, Buchy D, Gassmann M, Hoener MC et al.. (2009) The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proc Natl Acad Sci USA, 106 (47): 20081-6. [PMID:19892733]

3. Espinoza S, Salahpour A, Masri B, Sotnikova TD, Messa M, Barak LS, Caron MG, Gainetdinov RR. (2011) Functional interaction between trace amine-associated receptor 1 and dopamine D2 receptor. Mol Pharmacol, 80 (3): 416-25. [PMID:21670104]

4. Maguire JJ, Parker WA, Foord SM, Bonner TI, Neubig RR, Davenport AP. (2009) International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature. Pharmacol Rev, 61 (1): 1-8. [PMID:19325074]

5. Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, Durkin S, Zbinden KG, Norcross R, Meyer CA et al.. (2011) TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proc Natl Acad Sci USA, 108 (20): 8485-90. [PMID:21525407]

6. Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S et al.. (2004) 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med, 10 (6): 638-42. [PMID:15146179]

7. Stalder H, Hoener MC, Norcross RD. (2011) Selective antagonists of mouse trace amine-associated receptor 1 (mTAAR1): discovery of EPPTB (RO5212773). Bioorg Med Chem Lett, 21 (4): 1227-31. [PMID:21237643]

8. Xie Z, Miller GM. (2009) Trace amine-associated receptor 1 as a monoaminergic modulator in brain. Biochem Pharmacol, 78 (9): 1095-104. [PMID:19482011]