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MDMA (ecstasy) inhibition of MAO type A and type B: comparisons with fenfluramine and fluoxetine (Prozac).

E T Leonardi, Efrain C. Azmitia

Neuropsychopharmacology July 1994 DOI: 10.1038/npp.1994.26 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics In vitro enzyme kinetics study Peer reviewed
Population Rat brain homogenates
Interventions MDMA fenfluramine fluoxetine
Measures Ki, IC50
Topics MDMA
Key points MDMA preferentially inhibits MAO-A (IC50 = 44 micromol/L) over MAO-B (IC50 = 370 micromol/L) in rat brain homogenates, which the authors state should increase extracellular serotonin. Fenfluramine's effects do not appear to involve MAO inhibition, and combining fluoxetine with MDMA at their IC50 values produced no greater MAO inhibition than either drug alone.

Abstract

3,4-Methylenedioxymethamphetamine (MDMA), a serotonin (5-HT) neurotoxin, has been shown to promote the release of serotonin (5-HT) and block its reuptake. The increased buildup of extracellular 5-HT should normally be degraded by monoamine oxidase (MAO). The effects of both enantiomers of MDMA were examined on MAO-A and monoamine oxidase-B (MAO-B) activity in rat brain homogenates. Both enantiomers competitively inhibited 5-HT catabolism by rat brain MAO-A. The Ki of MDMA for MAO-A was 22 mumol/L. A mixed type of inhibition by MDMA was observed for phenethylamine catabolism by MAO-B for both optical antipodes. Logistical analysis of concentration response curves for MDMA inhibition of MAO-A and MAO-B show an IC50 of 44 mumol/L for inhibition of MAO-A by MDMA. The IC50 value of MDMA inhibition of MAO-B was 370 mumol/L, showing a selective potency for MAO-A inhibition. The MAO inhibitory properties of fenfluramine (FEN) and fluoxetine (FLUOX) were compared to those of MDMA. The rank order potency of these drugs for MAO-A inhibition was MDMA > FLUOX > FEN, whereas for MAO-B inhibition, FLUOX > MDMA > FEN. A combination of FLUOX and MDMA at their respective IC50 did not inhibit MAO activity more than either drug alone at equivalent concentrations. These results indicate that the actions of FEN do not appear to involve MAO inhibition. MDMA (ecstasy) produced a preferential inhibition of MAO-A (IC50 = 44 mumol/L), which should increase extracellular 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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