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Molecular Pharmacology

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Trace Amine-Associated Receptors as Emerging Therapeutic Targets

Tatyana D. Sotnikova, Marc G. Caron and Raul R. Gainetdinov
Molecular Pharmacology August 2009, 76 (2) 229-235; DOI: https://doi.org/10.1124/mol.109.055970
Tatyana D. Sotnikova
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Marc G. Caron
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Raul R. Gainetdinov
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Abstract

Endogenous trace amines (TAs) of unknown biological function are structurally related to classic monoaminergic neurotransmitters and found at low concentrations in the mammalian brain. Their recently discovered group of G protein-coupled receptors, trace amine-associated receptors (TAARs), may represent putative targets not only for trace and other amines but also for a variety of monoaminergic compounds, including amphetamines and monoamine metabolites. The trace amine-associated receptor 1 (TAAR1), which is in part associated with the monoaminergic neuronal circuitry controlling various functions, including movement, is the best characterized of the class, although little is known about its regulation and function. Here we review the pharmacology and biochemical properties of the TAAR1 and its physiological functions as revealed in studies involving knockout mice lacking this receptor. Potential therapeutic applications of future selective TAAR1 agonists and antagonists are also discussed. Although understanding of biology and functions mediated by other TAARs is still in its infancy, it is expected that further characterization of the functional roles and biochemical properties of TAARs and identification of endogenous and exogenous ligands will eventually promote these receptors as an attractive class of targets to correct monoaminergic processes that could be dysfunctional in a host of disorders of brain and periphery.

Footnotes

  • This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant NS19576]; the National Institutes of Health National Institute on Drug Abuse [Grant 1U01-DA022950]; and a research grant from F. Hoffmann-La Roche Ltd. (Basel, Switzerland).

  • ABBREVIATIONS: GPCR, G protein-coupled receptor; β-PEA, β-phenylethylamine; ADHD, attention deficit hyperactivity disorder; DAT, dopamine transporter; TA, trace amine; TAAR, trace amine-associated receptor; MDMA, 3,4-methylenedioxymethamphetamine; CNS, central nervous system; 3-MT, 3-methoxytyramine; 4-MT, 4-methoxytyramine; COMT, catechol-O-methyl transferase; T1AM, 3-iodothyronamine; DA, dopamine; βarr2, β-arrestin2; GFP, green fluorescent protein; β2-AR, β2-adrenergic receptor; BRET, bioluminescence resonance energy transfer; KO, knockout.

    • Accepted April 23, 2009.
    • Received March 6, 2009.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 76 (2)
Molecular Pharmacology
Vol. 76, Issue 2
1 Aug 2009
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Trace Amine-Associated Receptors as Emerging Therapeutic Targets

Tatyana D. Sotnikova, Marc G. Caron and Raul R. Gainetdinov
Molecular Pharmacology August 1, 2009, 76 (2) 229-235; DOI: https://doi.org/10.1124/mol.109.055970

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Trace Amine-Associated Receptors as Emerging Therapeutic Targets

Tatyana D. Sotnikova, Marc G. Caron and Raul R. Gainetdinov
Molecular Pharmacology August 1, 2009, 76 (2) 229-235; DOI: https://doi.org/10.1124/mol.109.055970
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