Drug effects on distribution of [3H]3,4-methylenedioxymethamphetamine in mice.
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.
Hashimoto
K
K
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.
Maeda
H
H
Hirai
K
K
Goromaru
T
T
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D017374:Paroxetine / Q000494:pharmacology; D014018:Tissue Distribution / Q000187:drug effects
D017374:Paroxetine; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine