Discriminative Stimulus Effects of Substituted Tryptamines in Rats
ACS Pharmacology & Translational Science – December 29, 2020
Source: OpenAlex
Summary
All tested novel substituted tryptamines exhibited hallucinogen-like effects, fully substituting for the discriminative stimulus of 2,5-dimethoxy-4-methylamphetamine (DOM). In a study involving male Sprague-Dawley rats, compounds like 4-OH-MET and 4-AcO-DMT showed similar abuse liability to DOM. Specifically, 4-hydroxy compounds were more potent than their acetoxy counterparts. Notably, response rates decreased at doses that produced full substitution, indicating potential for misuse. These findings highlight important implications for pharmacology and forensic toxicology concerning emerging psychoactive substances.
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-N,N-diethyltryptamine (4-AcO-DET), 4-hydroxy-N-methyl-N-ethyltryptamine (4-OH-MET), 4-hydroxy-N,N-diethyltryptamine (4-OH-DET), 4-acetoxy-N-methyl-N-isopropyltryptamine (4-AcO-MiPT), 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT), 4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DiPT), and 4-hydroxy-N,N-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 N,N-diisopropyl compounds were less potent than the dimethyl, diethyl, N-methyl-N-ethyl, and N-methyl-N-isopropyl compounds.