Effects of the enantiomers of MDA, MDMA and related analogues on [3H]serotonin and [3H]dopamine release from superfused rat brain slices.
M P Johnson, Andrew J. Hoffman, D E Nichols
European Journal of Pharmacology December 16, 1986 DOI: 10.1016/0014-2999(86)90615-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro pharmacology study Peer reviewed |
|---|---|
| Population | Rat hippocampal slices and rat caudate nucleus slices |
| Interventions | MDA BDB MDMA MBDB |
| Topics | MDMA Serotonin |
| Key points | All test compounds released [3H]serotonin similarly in the micromolar range with no significant stereoselectivity, but dopamine release differed: N-methylation of racemic MDA reduced dopamine release, side-chain extension from alpha-methyl to alpha-ethyl abolished it, and S-(+)-isomers of MDA and MDMA showed stereoselectivity. The authors suggest serotonin release may play a more important role in the mechanism of action than dopamine release. |
Abstract
The primary amines 3,4-methylenedioxyamphetamine (MDA), and 1-(1,3-benzodioxol-5-yl)-2-butanamine (BDB) were measured for efficacy in release of [3H]serotonin (5-HT) from rat hippocampal slices, and release of [3H]dopamine (DA) from rat caudate nucleus slices. The N-methyl derivatives of MDA and BDB, MDMA and MBDB, respectively, and the optical antipodes of these four agents were compared in this paradigm. All of the test compounds demonstrated a similar efficacy of [3H]5-HT release in the micromolar concentration range. No significant stereoselectivity was seen in measurements of 5-HT release. However, striking differences were found between the test compounds when [3H]DA release was studied. N-methylation of racemic MDA resulted in a decreased ability to release DA, while side chain extension from alpha-methyl to alpha-ethyl completely abolished this activity. Stereoselectivity for the S-(+)-isomers of MDA and MDMA was also demonstrated in the DA release studies. Correlation of these biochemical findings with human subjective reports indicates that serotonin release may play a more important role in the mechanism of action than does dopamine release.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proceedings of the National Academy of Sciences March 1, 1992
- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Neurotoxicity of MDMA and Related Compounds: Anatomic Studiesa Annals of the New York Academy of Sciences October 1, 1990
- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
and 135 more in the library
Cites 4
- Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class Journal of Medicinal Chemistry October 1, 1986
- Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Journal of Medicinal Chemistry May 1, 1982
- MDA-ASSISTED PSYCHOTHERAPY WITH NEUROTIC OUTPATIENTS The Journal of Nervous and Mental Disease October 1, 1976
- 3,4-Methylenedioxymethamphetamine (MDMA): stereoselective interactions at brain 5-HT1 and 5-HT2 receptors. Psychopharmacology 1986