Investigation of MDMA-related agents in rats trained to discriminate MDMA from saline.
Richard A Glennon, R Higgs
Pharmacology, Biochemistry, and Behavior November 1, 1992 DOI: 10.1016/0091-3057(92)90405-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study in rats Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats trained to discriminate MDMA from saline |
| Interventions | MDMA PMMA MDMA analogs |
| Dose | 1.5 mg/kg MDMA (training dose); PMMA ED50 = 0.2 mg/kg; MDMA ED50 = 0.76 mg/kg |
| Topics | MDMA |
| Keywords | Animals Rats, sprague-dawley Methamphetamine N-methyl-3,4-methylenedioxyamphetamine Male Discrimination, psychological |
| Key points | Most MDMA analogs produced only partial (50-60%) MDMA-appropriate responding and failed to generalize, while PMMA produced over 80% MDMA-appropriate responding and was roughly three times more potent than MDMA (ED50 0.2 vs 0.76 mg/kg). The authors argue that an intact methylenedioxy ring is not required for MDMA-like activity and that ring-opened MDMA metabolites may contribute to MDMA's effects. |
Abstract
To determine whether metabolite-related analogs of N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) produce stimulus effects similar to those of the parent compound, and to determine the structural requirements associated with the MDMA stimulus, several MDMA analogs were examined in tests of stimulus generalization using rats trained to discriminate 1.5 mg/kg MDMA from saline. Although several of the analogs produced up to 50-60% MDMA-appropriate responding, none [with the exception of N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA)] resulted in stimulus generalization. The partial generalization, coupled with the possible reduced ability of certain of the agents to penetrate the blood-brain barrier relative to MDMA, suggests that these agents are not behaviorally inactive. PMMA, although not a metabolite of MDMA, is closely related in chemical structure to MDMA and its metabolites; PMMA produces > 80% MDMA-appropriate responding and is approximately three times more potent (ED50 = 0.2 mg/kg) than MDMA itself (ED50 = 0.76 mg/kg). PMMA is a newer scheduled substance with an as yet unknown mechanism of action; however, on the basis of the stimulus generalization observed PMMA may share some behavioral and mechanistic similarity with MDMA. These results also indicate that an intact methylenedioxy ring, such as that found in MDMA but absent in PMMA, is not a prerequisite for MDMA-like activity and further support the notion that ring-opened MDMA metabolites may produce effects that contribute to the actions of MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 15
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- 3,4‐methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein Synapse July 14, 2004
- Initial characterization of PMMA as a discriminative stimulus. Pharmacology, Biochemistry, and Behavior 1997
- PMMA-stimulus generalization to the optical isomers of MBDB and 3,4-DMA. Pharmacology, Biochemistry, and Behavior 2001
- α-Ethyltryptamine: A Ratiocinatory Review of a Forgotten Antidepressant. ACS Pharmacology & Translational Science December 8, 2023
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Cites 8
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- Further studies on N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a discriminative stimulus: antagonism by 5-hydroxytryptamine3 antagonists. Pharmacology, Biochemistry, and Behavior December 1992
- The neurochemical and stimulatory effects of putative metabolites of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine in rats. Pharmacology, Biochemistry, and Behavior July 1991
- Metabolism of methylenedioxymethamphetamine: formation of dihydroxymethamphetamine and a quinone identified as its glutathione adduct. Journal of Pharmacology and Experimental Therapeutics August 1, 1990
- Stimulus effects of N-monoethyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDE) and N-hydroxy-1-(3,4-methylenedioxyphenyl)-2-aminopropane (N-OH MDA) in rats trained to discriminate MDMA from saline. Pharmacology, Biochemistry, and Behavior August 1989
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