Drug effects on distribution of [3H]3,4-methylenedioxymethamphetamine in mice.

doi:10.1016/0926-6917(93)90057-w

Drug effects on distribution of [3H]3,4-methylenedioxymethamphetamine in mice.

European Journal of Pharmacology April 1, 1993 DOI: 10.1016/0926-6917(93)90057-w (opens in new tab)

Study at a glance

Characteristics	Animal study Peer reviewed
Population	Mice
Interventions	MDMA Paroxetine MDA 1-piperonylpiperazine N alpha-dimethylpiperonylamine 6-nitroquipazine Fluoxetine Clomipramine GBR 12909 Desipramine Piperonylacetone Piperonyl butoxide Piperonyl isobutyrate
Dose	MDMA 15 mg/kg (carrier) or approximately 70 ng/kg ([3H]MDMA tracer); paroxetine 10 mg/kg i.p.
Topics	MDMA
Key points	Paroxetine pretreatment and several compounds bearing the 3,4-methylenedioxyphenyl (piperonyl) group increased brain radioactivity 60 minutes after tracer [3H]MDMA in mice, an effect the authors attribute in part to inhibited metabolism of MDMA to radioactive metabolites and suggest may involve a specific mechanism for the methylenedioxyphenyl group.

Abstract

The present study was undertaken to examine the drug interactions between 3,4-methylenedioxymethamphetamine (MDMA) and paroxetine or several compounds including the 3,4-methylenedioxybenzyl (piperonyl) group in mice. The time course of radioactivity in the mouse brain after i.v. administration of the tracer amount (approximately 70 ng/kg) of [3H]MDMA was altered significantly by coinjection of carrier MDMA (15 mg/kg) or by pretreatment with paroxetine (10 mg/kg, i.p., 5 min). Furthermore, the radioactivity in the brain 60 min after injection of [3H]MDMA was increased significantly by pretreatment with paroxetine, but not by pretreatment with 6-nitroquipazine, fluoxetine, clomipramine, GBR 12909 or desipramine, indicating that paroxetine-induced alteration of the brain radioactivity was not due to the inhibitory effect of 5-hydroxytryptamine (5-HT) uptake of paroxetine. The radioactivity in the brain 60 min after injection of [3H]MDMA was increased significantly by pretreatment with 3,4-methylenedioxyamphetamine (MDA), MDMA, 1-piperonylpiperazine and N, alpha-dimethylpiperonylamine, but not by pretreatment with piperonylacetone, piperonyl butoxide and piperonyl isobutyrate. HPLC analyses indicated that the alteration of brain radioactivity 60 min after injection of [3H]MDMA was, in part, due to inhibition in the metabolism of [3H]MDMA to radioactive metabolite(s). The present results suggest that a specific mechanism for the 3,4-methylenedioxyphenyl group which rapidly alters the disposition and metabolism of [3H]MDMA may exist in brain and peripheral organs of mice.

Comparable studies

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

Study	Year	Design
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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