Stereochemistry of the metabolism of MDMA to MDA.
Robert L. Fitzgerald, Robert V. Blanke, John A. Rosecrans, Richard A Glennon
Life Sciences 1989 DOI: 10.1016/0024-3205(89)90138-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal pharmacokinetic study Peer reviewed |
|---|---|
| Population | Rats (male, food-deprived male, female, and postpartum female) and mice dosed with racemic MDMA |
| Dose | 40 mg/kg |
| Duration | Blood sampled four hours after dosing |
| Topics | MDMA |
| Key points | After a 40 mg/kg subcutaneous dose of racemic MDMA in rats, plasma analyzed four hours later contained both MDMA isomers plus the metabolites S(+) and R(-)-MDA. In every group dosed with racemic MDMA, including mice, S(+)-MDA levels exceeded R(-)-MDA levels. The authors suggest this may be significant given reports that S(+)-MDMA is the more neurotoxic isomer. |
Abstract
The chiral derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (LTPC) was used to form diastereomers of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) which were resolved on an achiral gas chromatographic column using a mass spectrometer as a detector. Rats were subcutaneously dosed with 40 mg/kg of (+/-) MDMA.HCl and blood was obtained by decapitation four hours after dosing. Plasma was separated and extracted. The extract was derivatized on-column with LTPC. In addition to the two MDMA isomers, the demethylated metabolites, S(+) and R(-)-MDA were identified. In all experimental groups (male rats, food deprived male rats, female rats, post partum female rats, and mice) dosed with racemic MDMA, higher levels of the S(+) isomer of MDA relative to the R(-) MDA isomer were observed. This may be significant since it has been shown that the S(+) isomer of MDMA is the more neurotoxic isomer of the racemic drug of abuse MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 12
- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- Stereoselective pharmacokinetics of 3,4‐methylenedioxymethamphetamine in the rat Chirality 1990
- Biochemical, pharmacological, and toxic effects of n-metil 3,4-methylenedioxyamphetamine - "ecstasy" Vojnosanitetski Pregled 2005
- Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). Toxicology and Applied Pharmacology July 1, 2008
- Sex differences in the neurochemical and functional effects of MDMA in Sprague-Dawley rats. Psychopharmacology January 2007
and 7 more in the library
Cites 17
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
- Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. Biochemical Pharmacology July 15, 1987
- The Complications of 'Ecstasy' (MDMA) JAMA March 18, 1988
and 12 more in the library