Etk. Leonardi et Ec. Azmitia, MDMA (ECSTASY) INHIBITION OF MAO TYPE-A AND TYPE-B - COMPARISONS WITHFENFLURAMINE AND FLUOXETINE (PROZAC), Neuropsychopharmacology, 10(4), 1994, pp. 231-238
3,-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 norma
lly be degraded by monoamine oxidase (MAO). The effects of both enanti
omers of MDMA were examined on MAO-A and monoamine oxidase-B (MAO-B) a
ctivity in rat brain homogenates. Both enantiomers competitively inhib
ited 5-HT catabolism by rat brain MAO-A. The K-i of MDMA for MAO-A was
22 mu mol/L. A mixed type of inhibition by MDMA was observed for phen
ethylamine 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 mu mol/L for inhibition of MAO-A by MDMA
. The IC50 value of MDMA inhibition of MAO-B was 370 mu mol/L, showing
a selective potency for MAO-A inhibition. The MAO inhibitory properti
es of fenfluramine (FEN) and fluoxetine (FLUOX) were compared to those
of MDMA. The rank order potency of these drugs for MAO-A inhibition w
as MDMA>FLUOX>FEN, whereas for MAO-B inhibition, FLUOX>MDMA>FEN. A com
bination of FLUOX and MDMA at their respective IC50 did not inhibit MA
O activity more than either drug alone at equivalent concentrations. T
hese 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 mu mol/L), which should increase extracellular 5-HT.
This may explain ifs high toxicity potential. Finally, FLUOX (Prozac)
showed an inhibition of MAO-B (IC50 = 80 mu mol/L, which may increase
the intracellular content of 5-HT. This may contribute to its therapeu
tic potential. In contrast, FEN appears to be a poor inhibitor of both
MAO-A and MAO-B.