Methylenedioxymethamphetamine-like discriminative stimulus effects of pyrrolidinyl cathinones in rats
Michael B Gatch, Michael J Forster
Journal of Psychopharmacology July 1, 2020 DOI: 10.1177/0269881120914213 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal drug discrimination study Peer reviewed |
|---|---|
| Population | Sprague-Dawley rats trained to discriminate 1.5 mg/kg racemic MDMA from vehicle |
| Interventions | α-pyrrolidinopropiophenone 4′-methyl-α-pyrrolidinopropiophenone (4′-MePPP) α-pyrrolidinobutiophenone 3′ 4′-methylenedioxy-α-pyrrolidinobutyrophenone (MD-PBP) α-pyrrolidinovalerophenone 3 4-methylenedioxy-pyrovalerone (MDPV) α-pyrrolidinopentiothiophenone α-pyrrolidinohexiophenone 4′-methyl-α-pyrrolidinohexiophenone (4′-MePHP) |
| Topics | MDMA |
| Key points | Many pyrrolidinyl cathinones produced MDMA-appropriate responding in rats, ranging from 44% to 99.8%, with the degree depending on alpha side chain length and phenyl-ring substitution. The authors argue that pyrrolidine substitution reduces serotonergic and MDMA-like effects, while phenyl-ring substitutions can restore MDMA-like responding only in compounds with short alpha side chains. |
Abstract
Background: Synthetic cathinone derivatives are used as alternatives both for stimulant drugs such as cocaine and methamphetamine and for club drugs such as 3,4-methylenedioxymethamphetamine (MDMA), but little is known about their MDMA-like subjective effects.
Methods: In order to determine their similarity to MDMA, the discriminative stimulus effects of 10 pyrrolidinyl cathinones (α-pyrrolidinopropiophenone, 4′-methyl-α-pyrrolidinopropiophenone (4′-MePPP), α-pyrrolidinobutiophenone, 3′,4′-methylenedioxy-α-pyrrolidinobutyrophenone (MD-PBP), α-pyrrolidinovalerophenone, 3,4-methylenedioxy-pyrovalerone (MDPV), α-pyrrolidinopentiothiophenone, napthylpyrovalerone (naphyrone), α-pyrrolidinohexiophenone, and 4′-methyl-α-pyrrolidinohexiophenone (4′-MePHP)) were assessed in Sprague–Dawley rats trained to discriminate 1.5 mg/kg racemic ±-MDMA from vehicle.
Results: Compounds with no substitutions on the phenyl ring and the thiophene produced 44–67% MDMA-appropriate responding. In contrast, the substituted pyrrolidinyl cathinones produced a range of MDMA-appropriate responding dependent upon the length of the alpha side chain. 4′-MePPP, with a single carbon on the alpha position, produced 99.8% MDMA-appropriate responding, MD-PBP (two carbons) produced 83%, naphyrone (three carbons) produced 71%, MDPV (three carbons) produced, 66%, and 4′-MePHP (four carbons) produced 47%.
Conclusions: Many cathinone compounds have discriminative stimulus effects similar to those of MDMA. However, the pyrrolidine substitution appears to reduce serotonergic effects, with a commensurate decrease in MDMA-like effects. Substitutions on the phenyl ring appear to be able to restore MDMA-like responding, but only in compounds with short alpha side chains. These findings agree with earlier findings of increasing dopaminergic effects and stronger reinforcing effects with increasing side chain. Assessment of more compounds is necessary to establish the replicability/robustness of this phenomenon. These findings may be of use in predicting which compounds will have MDMA/club drug-like effects versus psychostimulant-like effects.