MDMA (Ecstasy) Inhibition of MAO Type A and Type B: Comparisons with Fenfluramine and Fluoxetine (Prozac)

Leonardi, Efthimia T. Kokotos; Azmitia, Efrain C.

doi:10.1038/npp.1994.26

Cited by 146 publications

(94 citation statements)

References 33 publications

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“…MDMA-induced 5-HT release therefore appears to play a major role in the release of dopamine. When one adds the known e ects of MDMA on dopamine uptake inhibition (Steele et al, 1987) and MAO inhibition (Leonardi & Azmitia, 1994) then it becomes plausible to suggest that carriermediated exchange need not be a major determinant in the increase of extracellular dopamine which follows MDMA administration, a suggestion supported by recent in vitro studies (Crespi et al, 1997). Further support for this proposal comes from our study on the e ect of clomethiazole.…”

Section: Discussionsupporting

confidence: 71%

“…These changes on dopamine metabolites are probably the results of MDMA blocking dopamine re-uptake (causing less dopamine to be metabolized to DOPAC) and also by inhibiting monoamine oxidase (MAO). Dopamine is preferentially metabolized by MAO-A in the rat striatum in vivo (Kato et al, 1986) and MDMA acts as a competitive inhibitor of MAO-A activity (Leonardi & Azmitia, 1994). An additional explanation of the decrease in DOPAC and HVA would be a reduction in dopamine synthesis following MDMA.…”

Section: Discussionmentioning

confidence: 99%

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Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration

Colado

O’Shea

Granados

et al. 1999

British J Pharmacology

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1 We investigated whether dopamine plays a role in the neurodegeneration of 5-hydroxytryptamine (5-HT) nerve endings occurring in Dark Agouti rat brain after 3,4-methylenedioxymethamphetamine (MDMA or`ecstasy') administration. 2 Haloperidol (2 mg kg 71 i.p.) injected 5 min prior and 55 min post MDMA (15 mg kg 71 i.p.) abolished the acute MDMA-induced hyperthermia and attenuated the neurotoxic loss of 5-HT 7 days later. When the rectal temperature of MDMA+haloperidol treated rats was kept elevated, this protective e ect was marginal. 3 MDMA (15 mg kg 71 ) increased the dopamine concentration in the dialysate from a striatal microdialysis probe by 800%. L-DOPA (25 mg kg 71 i.p., plus benserazide, 6.25 mg kg 71 i.p.) injected 2 h after MDMA (15 mg kg 71 ) enhanced the increase in dopamine in the dialysate, but subsequent neurodegeneration was unaltered. L-DOPA (25 mg kg 71 ) injected before a sub-toxic dose of MDMA (5 mg kg 71 ) failed to induce neurodegeneration. 4 The MDMA-induced increase in free radical formation in the hippocampus (indicated by increased 2,3-and 2,5-dihydroxybenzoic acid in a microdialysis probe perfused with salicylic acid) was unaltered by L-DOPA. 5 The neuroprotective drug clomethiazole (50 mg kg 71 i.p.) did not in¯uence the MDMA-induced increase in extracellular dopamine. 6 These data suggest that previous observations on the protective e ect of haloperidol and potentiating e ect of L-DOPA on MDMA-induced neurodegeneration may have resulted from e ects on MDMA-induced hyperthermia. 7 The increased extracellular dopamine concentration following MDMA may result from e ects of MDMA on dopamine re-uptake, monoamine oxidase and 5-HT release rather than aǹ amphetamine-like' action on dopamine release, thus explaining why the drug does not induce degeneration of dopamine nerve endings.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration

Colado

O’Shea

Granados

et al. 1999

British J Pharmacology

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show abstract

“…MDMA also has been reported to interfere with 5-HT metabolism (Leonardi and Azmitia, 1994). Thus, an action of MDMA to increase the intraneuronal accumulation of 5-HT may also contribute to the magnitude of 5-HT efflux evoked by MDMA.…”

Section: Serotonergic Neuronsmentioning

confidence: 99%

Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons

Gudelsky

Yamamoto

2008

Pharmacology Biochemistry and Behavior

120

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Abstract3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative and a popular drug of abuse that exhibits mild hallucinogenic and rewarding properties and engenders feelings of connectedness and openness. The unique psychopharmacological profile of this drug of abuse most likely is derived from the property of MDMA to promote the release of dopamine and serotonin (5-HT) in multiple brain regions. The present review highlights primarily data from studies employing in vivo microdialysis that detail the actions of MDMA on the release of these neurotransmitters. Data from in vivo microdialysis experiments indicate that MDMA, like most amphetamine derivatives, increases the release of dopamine in the striatum, n. accumbens and prefrontal cortex. However, the release of dopamine evoked by MDMA in each of these brain regions appears to be modulated by concomitantly released 5-HT and the subsequent activation of 5-HT2A/C or 5-HT2B/C receptors. In addition to its stimulatory effect on the release of monoamines, MDMA also enhances the release of acetylcholine in the striatum, hippocampus and prefrontal cortex, and this cholinergic response appears to be secondary to the activation of histaminergic, dopaminergic and/or serotonergic receptors. Beyond the acute stimulatory effect of MDMA on neurotransmitter release, MDMA also increases the extracellular concentration of energy substrates, e.g., glucose and lactate in the brain. In contrast to the acute stimulatory actions of MDMA on the release of monoamines and acetylcholine, the repeated administration of high doses of MDMA is thought to result in a selective neurotoxicity to 5-HT axon terminals in the rat. Additional studies are reviewed that focus on the alterations in neurotransmitter responses to pharmacological and physiological stimuli that accompany MDMA-induced 5-HT neurotoxicity.

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“…MDMA binds to the 5-HT reuptake transporter and, inside axon terminals, causes an acute and powerful release of neurotransmitters (mainly 5-HT, but also noradrenaline and dopamine) from storage vesicles (Green et al, 1995;Sulzer et al, 2005). MDMA also contributes to a steady concentration of these neurotransmitters in the synaptic cleft by partially inhibiting their oxidation through monoamine oxidase (MAO) while inside nerve endings and by blocking their reuptake into nerve terminals (Leonardi and Azmitia, 1994;Green et al, 2003). During the phase of abrupt increase of the extravesicular levels of monoamine neurotransmitters inside nerve endings, a large amount is metabolized by MAO.…”

Section: Introductionmentioning

confidence: 99%

Monoamine Oxidase-B Mediates Ecstasy-Induced Neurotoxic Effects to Adolescent Rat Brain Mitochondria

Alves¹,

Summavielle²,

Alves³

et al. 2007

J. Neurosci.

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MDMA (Ecstasy) Inhibition of MAO Type A and Type B: Comparisons with Fenfluramine and Fluoxetine (Prozac)

Abstract: Received November 7, 1993; revised February 16, 1994; accepted February 17, 1994.

Cited by 146 publications

References 33 publications

Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration

Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration

Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons

Monoamine Oxidase-B Mediates Ecstasy-Induced Neurotoxic Effects to Adolescent Rat Brain Mitochondria

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