Trace Amine-Associated Receptor 1 (TAAR1)
Trace amines (TAs) are a class of endogenous amines that traditionally include compounds such as β-phenylethylamine (b-PEA), tyramine, tryptamine, octopamine, and synephrine (Fig. 1) (Berry 2004). Trace amines are characterized by their trace levels in the brain, their lack of vesicular storage, and their fast metabolism. These molecules are structurally related to the classic monoamines (dopamine, norepinephrine, and serotonin) and share similar synthetic and degradation pathways. TAs are synthesized by the action of L-amino acid decarboxylase and are degraded primarily by monoamine oxidases (MAO-A and MAO-B) (Fig. 2). TAs were initially discovered over 100 years ago and are present in several organisms (Grandy 2007). In invertebrates, octopamine and tyramine serve as major neurotransmitters, functionally replacing the role of epinephrine and norepinephrine found in vertebrates. However, in vertebrates, in particular in mammals,...
KeywordsPrefrontal Cortex Ventral Tegmental Area Partial Agonist Dorsal Raphe NREM Sleep
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- Barak LS, Salahpour A, Zhang X, Masri B, Sotnikova TD, Ramsey AJ, et al. Pharmacological characterization of membrane-expressed human trace amine-associated receptor 1 (TAAR1) by a bioluminescence resonance energy transfer cAMP biosensor. Mol Pharmacol. 2008;74:585–94. doi:10.1124/mol.108.048884. mol.108.048884. [pii].CrossRefPubMedPubMedCentralGoogle Scholar
- Black SW, Schwartz MD, Chen TM, Hoener MC, Kilduff TS. Trace amine-associated receptor 1 agonists as narcolepsy therapeutics. Biol Psychiatry. 2016. doi:10.1016/j.biopsych.2016.10.012.Google Scholar
- Bradaia A, Trube G, Stalder H, Norcross RD, Ozmen L, Wettstein JG, et al. The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proc Natl Acad Sci USA. 2009. doi:10.1073/pnas.0906522106. 0906522106 [pii].PubMedPubMedCentralGoogle Scholar
- Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, et al. Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Mol Pharmacol. 2001;60:1181–8.PubMedGoogle Scholar
- Cichero E, Espinoza S, Franchini S, Guariento S, Brasili L, Gainetdinov RR, et al. Further insights into the pharmacology of the human trace amine-associated receptors: discovery of novel ligands for TAAR1 by a virtual screening approach. Chem Biol Drug Des. 2014;84:712–20. doi:10.1111/cbdd.12367.CrossRefPubMedGoogle Scholar
- Lam VM, Rodríguez, Zhang T, Koh EJ, Carlsson J, Salahpour A. Discovery of tace amine-assoicated receptor 1 ligands by molecular docking screening against a homology model. Med Chem Comm. 2015;12:2216–2223. doi: 10.1039/C5MD00400DGoogle Scholar
- Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC. Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors. Genomics. 2005;85:372–85. doi:10.1016/j.ygeno.2004.11.010. S0888-7543(04)00316-7 [pii].CrossRefPubMedGoogle Scholar
- Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, et al. TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proc Natl Acad Sci USA. 2011;108:8485–90. doi:10.1073/pnas.1103029108. 1103029108 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
- Revel FG, Moreau JL, Gainetdinov RR, Ferragud A, Velazquez-Sanchez C, Sotnikova TD, et al. Trace amine-associated receptor 1 partial agonism reveals novel paradigm for neuropsychiatric therapeutics. Biol Psychiatry. 2012;72:934–42. doi:10.1016/j.biopsych.2012.05.014. S0006-3223(12)00459-3 [pii].CrossRefPubMedGoogle Scholar
- Revel FG, Moreau JL, Pouzet B, Mory R, Bradaia A, Buchy D, et al. A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight. Mol Psychiatry. 2013;18:543–56. doi:10.1038/mp.2012.57. mp201257 [pii].CrossRefPubMedGoogle Scholar
- Schwartz MD, Black SW, Fisher SP, Palmerston JB, Morairty SR, Hoener MC, et al. Trace amine-associated receptor 1 regulates wakefulness and EEG spectral composition. Neuropsychopharmacology. 2016. doi:10.1038/npp.2016.216.Google Scholar
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