Trace amine-associated receptor

Trace amine-associated receptors (TAARs), sometimes referred to as trace amine receptors (TAs or TARs), are a class of G protein-coupled receptors that were discovered in 2001.^[1]^[2] TAAR1, the first of six functional human TAARs, has gained considerable interest in academic and proprietary pharmaceutical research due to its role as the endogenous receptor for the trace amines phenethylamine, tyramine, and tryptamine – metabolic derivatives of the amino acids phenylalanine, tyrosine and tryptophan, respectively – ephedrine, as well as the synthetic psychostimulants, amphetamine, methamphetamine and methylenedioxymethamphetamine (MDMA, ecstasy).^[3]^[4]^[5]^[6]^[7]^[8] In 2004, it was shown that mammalian TAAR1 is also a receptor for thyronamines, decarboxylated and deiodinated relatives of thyroid hormones.^[5] TAAR2–TAAR9 function as olfactory receptors for volatile amine odorants in vertebrates.^[9]

^ Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, et al. (July 2001). "Trace amines: identification of a family of mammalian G protein-coupled receptors". Proceedings of the National Academy of Sciences of the United States of America. 98 (16): 8966–8971. doi:10.1073/pnas.151105198. PMC 55357. PMID 11459929.
^ Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, et al. (December 2001). "Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor". Molecular Pharmacology. 60 (6): 1181–1188. doi:10.1124/mol.60.6.1181. PMID 11723224.
^ Cite error: The named reference Miller was invoked but never defined (see the help page).
^ Lam VM, Espinoza S, Gerasimov AS, Gainetdinov RR, Salahpour A (September 2015). "In-vivo pharmacology of Trace-Amine Associated Receptor 1". European Journal of Pharmacology. 763 (Pt B): 136–142. doi:10.1016/j.ejphar.2015.06.026. PMID 26093041.
^ ^a ^b Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, et al. (June 2004). "3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone". Nature Medicine. 10 (6): 638–642. doi:10.1038/nm1051. PMID 15146179. S2CID 2389946.
^ Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.
^ Hart ME, Suchland KL, Miyakawa M, Bunzow JR, Grandy DK, Scanlan TS (February 2006). "Trace amine-associated receptor agonists: synthesis and evaluation of thyronamines and related analogues". Journal of Medicinal Chemistry. 49 (3): 1101–1112. doi:10.1021/jm0505718. PMID 16451074.
^ Grandy DK (December 2007). "Trace amine-associated receptor 1-Family archetype or iconoclast?". Pharmacology & Therapeutics. 116 (3): 355–390. doi:10.1016/j.pharmthera.2007.06.007. PMC 2767338. PMID 17888514.
^ Liberles SD (October 2015). "Trace amine-associated receptors: ligands, neural circuits, and behaviors". Current Opinion in Neurobiology. 34: 1–7. doi:10.1016/j.conb.2015.01.001. PMC 4508243. PMID 25616211. Roles for another receptor are supported by TAAR5-independent trimethylamine anosmias in humans [32]. ... Several TAARs detect volatile and aversive amines, but the olfactory system is capable of discarding ligand-based or function-based constraints on TAAR evolution. Particular TAARs have mutated to recognize new ligands, with almost an entire teleost clade losing the canonical amine-recognition motif. Furthermore, while some TAARs detect aversive odors, TAAR-mediated behaviors can vary across species. ... The ability of particular TAARs to mediate aversion and attraction behavior provides an exciting opportunity for mechanistic unraveling of odor valence encoding.
Figure 2: Table of ligands, expression patterns, and species-specific behavioral responses for each TAAR

[pmid11459929-1] Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, et al. (July 2001). "Trace amines: identification of a family of mammalian G protein-coupled receptors". Proceedings of the National Academy of Sciences of the United States of America. 98 (16): 8966–8971. doi:10.1073/pnas.151105198. PMC 55357. PMID 11459929.

[pmid11723224-2] Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, et al. (December 2001). "Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor". Molecular Pharmacology. 60 (6): 1181–1188. doi:10.1124/mol.60.6.1181. PMID 11723224.

[Miller-3] Cite error: The named reference Miller was invoked but never defined (see the help page).

[In-vivo_TAAR1-4] Lam VM, Espinoza S, Gerasimov AS, Gainetdinov RR, Salahpour A (September 2015). "In-vivo pharmacology of Trace-Amine Associated Receptor 1". European Journal of Pharmacology. 763 (Pt B): 136–142. doi:10.1016/j.ejphar.2015.06.026. PMID 26093041.

[pmid15146179-5] Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, et al. (June 2004). "3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone". Nature Medicine. 10 (6): 638–642. doi:10.1038/nm1051. PMID 15146179. S2CID 2389946.

[pmid15860375-6] Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.

[pmid16451074-7] Hart ME, Suchland KL, Miyakawa M, Bunzow JR, Grandy DK, Scanlan TS (February 2006). "Trace amine-associated receptor agonists: synthesis and evaluation of thyronamines and related analogues". Journal of Medicinal Chemistry. 49 (3): 1101–1112. doi:10.1021/jm0505718. PMID 16451074.

[pmid17888514-8] Grandy DK (December 2007). "Trace amine-associated receptor 1-Family archetype or iconoclast?". Pharmacology & Therapeutics. 116 (3): 355–390. doi:10.1016/j.pharmthera.2007.06.007. PMC 2767338. PMID 17888514.

[TAAR_2015_review_-_olfactory_TAARs-9] Liberles SD (October 2015). "Trace amine-associated receptors: ligands, neural circuits, and behaviors". Current Opinion in Neurobiology. 34: 1–7. doi:10.1016/j.conb.2015.01.001. PMC 4508243. PMID 25616211. Roles for another receptor are supported by TAAR5-independent trimethylamine anosmias in humans [32]. ... Several TAARs detect volatile and aversive amines, but the olfactory system is capable of discarding ligand-based or function-based constraints on TAAR evolution. Particular TAARs have mutated to recognize new ligands, with almost an entire teleost clade losing the canonical amine-recognition motif. Furthermore, while some TAARs detect aversive odors, TAAR-mediated behaviors can vary across species. ... The ability of particular TAARs to mediate aversion and attraction behavior provides an exciting opportunity for mechanistic unraveling of odor valence encoding.
Figure 2: Table of ligands, expression patterns, and species-specific behavioral responses for each TAAR

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