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Research ArticleNeuropharmacology

Abuse Liability Profile of Three Substituted Tryptamines

Michael B. Gatch, Michael J. Forster, Aaron Janowsky and Amy J. Eshleman
Journal of Pharmacology and Experimental Therapeutics July 2011, 338 (1) 280-289; DOI: https://doi.org/10.1124/jpet.111.179705
Michael B. Gatch
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Michael J. Forster
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Aaron Janowsky
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Amy J. Eshleman
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Abstract

The abuse liability profile of three synthetic hallucinogens, N,N-diisopropyltryptamine (DIPT), 5-N,N-diethyl-5-methoxytryptamine (5-MeO-DET), and 5-methoxy-α-methyltryptamine (5-MeO-AMT), was tested in rats trained to discriminate hallucinogenic and psychostimulant compounds, including cocaine, methamphetamine, 3,4-methylenedioxymethylamphetamine (MDMA), lysergic acid diethylamide (LSD), (−)-2,5-dimethoxy-4-methylamphetamine (DOM), and dimethyltryptamine (DMT). Because abused hallucinogens act at 5-hydroxytryptamine 1A (5-HT1A) and 5-HT2A receptors, and abused psychostimulants act at monoamine transporters, binding and functional activities of DIPT, 5-MeO-DET, and 5-MeO-AMT at these sites were also tested. DIPT fully substituted in rats trained to discriminate DMT (ED50 = 1.71 mg/kg) and DOM (ED50 = 1.94 mg/kg), but produced only 68% LSD-appropriate responding. 5-MeO-DET fully substituted for DMT (ED50 = 0.41 mg/kg) and produced 59% MDMA-appropriate responding. 5-MeO-AMT did not fully substitute for any of the training drugs, but produced 67% LSD-appropriate responding. None of the compounds produced substitution in rats trained to discriminate cocaine or methamphetamine. All three compounds showed activity at 5-HT1A and 5-HT2A receptors as well as blockade of reuptake by the serotonin transporter. In addition, 5-MeO-AMT produced low levels of serotonin release and low potency blockade of dopamine uptake. DIPT, 5-MeO-DET, and 5-MeO-AMT produced behavioral and receptor effects similar to those of abused hallucinogens, but were not similar to those of psychostimulants. DIPT and 5-MeO-DET may have abuse liability similar to known hallucinogens and may be hazardous because high doses produced activity and lethality.

Footnotes

  • This work was supported by the National Institutes of Health National Institute on Drug Abuse [Contract N01-DA2-8822] (Addiction Treatment Discovery Program; to M.J.F.); the National Institutes of Health National Institute on Drug Abuse [Interagency Agreement Y1-DA5007] and VA Merit and Career Scientist awards (to A.J.).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.111.179705.

  • ABBREVIATIONS:

    DIPT
    N,N-diisopropyltryptamine
    LSD
    lysergic acid diethylamide
    5-MeO-DET
    5-N,N-diethyl-5-methoxytryptamine
    5-MeO-AMT
    5-methoxy-α-methyltryptamine
    MDMA
    3,4-methylenedioxymethylamphetamine
    DOM
    (−)-2,5-dimethoxy-4-methylamphetamine
    DMT
    dimethyltryptamine
    DOI
    2,5-dimethoxy-4-iodoamphetamine
    8-OH-DPAT
    8-hydroxy-2-(di-n-propylamino)tetralin
    HEK
    human embryonic kidney
    IP-1
    inositol-monophosphate
    GTPγS
    guanosine 5′-O-[γ-thio]triphosphate
    WAY 100635
    N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide
    5-HT
    5-hydroxytryptamine (serotonin)
    AA
    arachadonic acid
    hDAT
    human dopamine transporter
    hSERT
    human serotonin transporter
    hNET
    norepinephrine transporter
    DMEM
    Dulbecco's modified Eagle's medium
    DMSO
    dimethylsulfoxide
    G418
    (2R,3S,4R,5R,6S)-5-amino-6-[(1R,2S,3S,4R,6S)-4,6-diamino-3-[(2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-methylaminooxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-2-(1-hydroxyethyl)oxane-3,4-diol
    RTI-55
    (−)-2β-carbomethoxy-3β-(4-iodophenyl)tropane.

  • Received January 20, 2011.
  • Accepted April 6, 2011.
  • U.S. Government work not protected by U.S. copyright
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Journal of Pharmacology and Experimental Therapeutics: 338 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 338, Issue 1
1 Jul 2011
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Research ArticleNeuropharmacology

Abuse Liability Profile of Three Substituted Tryptamines

Michael B. Gatch, Michael J. Forster, Aaron Janowsky and Amy J. Eshleman
Journal of Pharmacology and Experimental Therapeutics July 1, 2011, 338 (1) 280-289; DOI: https://doi.org/10.1124/jpet.111.179705

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Research ArticleNeuropharmacology

Abuse Liability Profile of Three Substituted Tryptamines

Michael B. Gatch, Michael J. Forster, Aaron Janowsky and Amy J. Eshleman
Journal of Pharmacology and Experimental Therapeutics July 1, 2011, 338 (1) 280-289; DOI: https://doi.org/10.1124/jpet.111.179705
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