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

    Fingerprint

    Amphetamines
    GTP-Binding Proteins
    Phenethylamines
    Dopamine
    N-Methyl-3,4-methylenedioxyamphetamine
    Ventral Tegmental Area
    Tyramine
    Biogenic Amines
    Methamphetamine
    Trace amine-associated receptor 1
    Dopaminergic Neurons
    Amphetamine
    Prefrontal Cortex
    Cocaine
    Cyclic AMP
    Adrenergic Receptors
    Epinephrine
    Catecholamines
    Amines
    Gastrointestinal Tract

    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)

    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

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

    Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects. Vol. 2 Elsevier Inc., 2016. p. 108-116.

    Research output: Chapter in Book/Report/Conference proceedingChapter

    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, Elsevier Inc., pp. 108-116. https://doi.org/10.1016/B978-0-12-800212-4.00010-8
    Grandy D. 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. Elsevier Inc. 2016. p. 108-116 https://doi.org/10.1016/B978-0-12-800212-4.00010-8
    Grandy, David. / Amphetamines Activate G-Protein Coupled Trace Amine-Associated Receptor 1 (TAAR1) : Implications for Understanding and Treating Psychostimulant Abuse. Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects. Vol. 2 Elsevier Inc., 2016. pp. 108-116
    @inbook{df3a3c5987694c32a7ff857fd945193b,
    title = "Amphetamines Activate G-Protein Coupled Trace Amine-Associated Receptor 1 (TAAR1): Implications for Understanding and Treating Psychostimulant Abuse",
    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.",
    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",
    author = "David Grandy",
    year = "2016",
    month = "4",
    day = "15",
    doi = "10.1016/B978-0-12-800212-4.00010-8",
    language = "English (US)",
    isbn = "9780128003756",
    volume = "2",
    pages = "108--116",
    booktitle = "Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects",
    publisher = "Elsevier Inc.",

    }

    TY - CHAP

    T1 - Amphetamines Activate G-Protein Coupled Trace Amine-Associated Receptor 1 (TAAR1)

    T2 - Implications for Understanding and Treating Psychostimulant Abuse

    AU - Grandy, David

    PY - 2016/4/15

    Y1 - 2016/4/15

    N2 - 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.

    AB - 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.

    KW - Agonist

    KW - Amphetamine

    KW - Antagonist

    KW - Catecholamine

    KW - Cyclic AMP (cAMP)

    KW - Degenerate oligonucleotide primer

    KW - False transmitter

    KW - G s

    KW - G-protein coupled receptor

    KW - Heterologous expression

    KW - Immune cells

    KW - Inverse agonist

    KW - Methamphetamine

    KW - Noncatecholic biogenic amine

    KW - Orphan receptor

    KW - Partial agonist

    KW - Pharmacophore

    KW - RNA in situ hybridization

    KW - Trace amines

    UR - http://www.scopus.com/inward/record.url?scp=84969590397&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84969590397&partnerID=8YFLogxK

    U2 - 10.1016/B978-0-12-800212-4.00010-8

    DO - 10.1016/B978-0-12-800212-4.00010-8

    M3 - Chapter

    SN - 9780128003756

    SN - 9780128002124

    VL - 2

    SP - 108

    EP - 116

    BT - Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects

    PB - Elsevier Inc.

    ER -