Discriminative Stimulus Effects of Substituted Tryptamines in Rats.

ACS Pharmacol Transl Sci

Diversion Control Division Drug and Chemical Evaluation Section, Drug Enforcement Administration Springfield, Virginia 22152, United States.

Published: April 2021

AI Article Synopsis

  • Novel synthetic compounds have been studied for their hallucinogenic effects and potential for abuse, with emphasis on eight tryptamines.
  • Male rats were trained to identify a specific compound, DOM, which served as a reference for evaluating the effects of the new compounds.
  • All compounds tested showed similar effects to DOM, indicating they may have comparable abuse potential, with variations in potency among the different chemical substitutions.

Article Abstract

Novel synthetic compounds have been available for decades as quasi-legal alternatives to controlled substances. The hallucinogen-like effects of eight novel substituted tryptamines were evaluated to determine their potential abuse liability. Male Sprague-Dawley rats were trained to discriminate 2,5-dimethoxy-4-methylamphetamine (DOM, 0.5 mg/kg, i.p., 30 min) from saline. 4-Acetoxy-,-diethyltryptamine (4-AcO-DET), 4-hydroxy--methyl--ethyltryptamine (4-OH-MET), 4-hydroxy-,-diethyltryptamine (4-OH-DET), 4-acetoxy--methyl--isopropyltryptamine (4-AcO-MiPT), 4-acetoxy-,-dimethyltryptamine (4-AcO-DMT), 4-hydroxy-,-dimethyltryptamine (4-OH-DMT, psilocin), 5-methoxy--methyl--isopropyltryptamine (5-MeO-MiPT), 4-acetoxy-,-diisopropyltryptamine (4-AcO-DiPT), and 4-hydroxy-,-diisopropyltryptamine (4-OH-DiPT) were tested for their ability to substitute for the discriminative stimulus effects of DOM. All test compounds fully substituted for DOM with potencies less than or equal to that of DOM. 4-OH-MET, 4-OH-DET, 4-OH-DMT, and 4-AcO-DMT decreased response rate at doses that fully substituted. Because the test compounds produced DOM-like discriminative stimulus effects, they may have similar abuse liability as DOM. 4-Acetoxy substituted compounds were less potent than 4-hydroxy substituted compounds, and the ,-diisopropyl compounds were less potent than the dimethyl, diethyl, -methyl--ethyl, and -methyl--isopropyl compounds.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033599PMC
http://dx.doi.org/10.1021/acsptsci.0c00173DOI Listing

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