Amphetamines Activate G-Protein Coupled Trace Amine-Associated Receptor 1 (TAAR1): Implications for Understanding and Treating Psychostimulant Abuse

David Grandy

    Research output: Chapter in Book/Report/Conference proceedingChapter

    Abstract

    Trace amine-associated receptor 1 (TAAR1) shares significant nucleotide and amino acid sequence identity with dopamine, adrenergic, and serotonergic receptors. Heterologously expressed in vitro, TAAR1 couples to cyclic adenosine monophosphate production via G s when exposed to molecules containing a phenylethylamine moiety. This pharmacophore is present in the endogenous noncatecholic biogenic "trace amines" phenylethylamine and p-tyramine, 3-iodothyronamine, the catecholamines dopamine, norepinephrine, and epinephrine, and the synthetic amines amphetamine, methamphetamine, parahydroxyamphetamine, and methylenedioxymethamphetamine (ecstasy). TAAR1 is expressed in glutamatergic neurons of the prefrontal cortex, dopamine-producing neurons of the ventral tegmental area, insulin-producing cells, discrete sections of the gastrointestinal tract, and immune cells. Due to its pharmacologic and anatomic profiles, TAAR1 is a target of commercial drug development with several TAAR1-selective compounds already reported. Behavioral studies involving TAAR1-selective ligands confirm modulating TAAR1-mediated signaling favorably alters rodent responses to amphetamines and cocaine. Consequently, TAAR1 must be considered an essential element of any comprehensive model of psychostimulant action.

    Original languageEnglish (US)
    Title of host publicationStimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects
    PublisherElsevier Inc.
    Pages108-116
    Number of pages9
    Volume2
    ISBN (Print)9780128003756, 9780128002124
    DOIs
    StatePublished - Apr 15 2016

    Keywords

    • Agonist
    • Amphetamine
    • Antagonist
    • Catecholamine
    • Cyclic AMP (cAMP)
    • Degenerate oligonucleotide primer
    • False transmitter
    • G s
    • G-protein coupled receptor
    • Heterologous expression
    • Immune cells
    • Inverse agonist
    • Methamphetamine
    • Noncatecholic biogenic amine
    • Orphan receptor
    • Partial agonist
    • Pharmacophore
    • RNA in situ hybridization
    • Trace amines

    ASJC Scopus subject areas

    • Medicine(all)

    Fingerprint Dive into the research topics of 'Amphetamines Activate G-Protein Coupled Trace Amine-Associated Receptor 1 (TAAR1): Implications for Understanding and Treating Psychostimulant Abuse'. Together they form a unique fingerprint.

  • Cite this

    Grandy, D. (2016). Amphetamines Activate G-Protein Coupled Trace Amine-Associated Receptor 1 (TAAR1): Implications for Understanding and Treating Psychostimulant Abuse. In Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects (Vol. 2, pp. 108-116). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-800212-4.00010-8