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.
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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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