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Trace amines are an endogenous group of amines structurally and metabolically related to classical monoamine neurotransmitters, such as dopamine, norepinephrine, and serotonin. Compared to the classical monoamines, they are present in trace concentrations. They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of metabolism. Although, they can be synthesized within parent monoamine neurotransmitter systems, there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.
Trace amines may play very significant roles in the coordination of biogenic monoamine-based synaptic physiology. At high concentrations, they have well-characterized presynaptic ‘‘amphetamine-like’’ effects on monoamine release, reuptake and biosynthesis; at lower concentrations, they possess postsynaptic modulatory effects that potentiate the activity of other neurotransmitters, particularly dopamine and serotonin. A family of G protein coupled receptors known as TAARs (trace amine associated receptors) has been characterized to be responsive to trace amines and structurally related psychoactive drugs, such as amphetamine, MDMA, LSD, and DMT. Like dopamine, noradrenaline, and serotonin, the trace amines have been implicated in a vast array of human disorders of affect and cognition, such as depression and schizophrenia.
A thorough review of trace amines and trace amine receptors that discusses the historical evolution of this research particularly well is that of Grandy.
Burchett SA, Hicks TP. The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain. Prog Neurobiol. 2006 Aug;79(5-6):223-46.
Burchett SA, Hicks TP. The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain. Prog Neurobiol. 2006 Aug;79(5-6):223-46.
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 Mar;85(3):372-85.
Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK. Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Mol Pharmacol. 2001 Dec;60(6):1181-8.
Davis, B.A., Boulton, A.A., 1994. The trace amines and their acidic metabolites in depression—an overview. Prog. Neuropsychopharmacol. Biol. Psychiatry 18, 17–45.
References for all endogenous human TAAR1 ligands are provided at List of trace amines
References for synthetic TAAR1 agonists can be found at TAAR1 or in the associated compound articles. For TAAR2 and TAAR5 agonists and inverse agonists, see TAAR for references.
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