Reduction of in vivo binding of [3H]paroxetine in mouse brain by 3,4-methylenedioxymethamphetamine.
The effects of 3,4-methylenedioxymethamphetamine (MDMA) on the in vivo binding of [3H]paroxetine, a potent and selective 5-hydroxytryptamine (5-HT; serotonin) uptake inhibitor, in the brain of the mouse were studied. The distribution of radioactivity in the brain of the mouse, after intravenous administration of [3H]paroxetine, was significantly altered by pretreatment with MDMA (15 mg/kg, i.p., 3 hr before). The hypothalamus/cerebellum and cerebral cortex/cerebellum ratios, as a function of time, were significantly decreased after the pretreatment with MDMA, indicating that the in vivo binding of [3H]paroxetine to uptake sites for 5-HT in the brain of the mouse was significantly decreased by MDMA. These ratios could reflect those of the total binding, to the non-specific binding and free ligand, since the cerebellum has very low levels of binding for [3H]paroxetine. Furthermore, these ratios decreased after pretreatment with MDMA, in a dose-dependent manner. However, the binding of [3H]paroxetine to membranes from the brain of the mouse in vitro was not altered by treatment with MDMA. The discrepancy between the in vivo binding and in vitro binding of [3H]paroxetine in the brain of the mouse is discussed.
Department of Radiopharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Fukuyama, Japan.
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Hashimoto
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Goromaru
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D017374:Paroxetine; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology; D012701:Serotonin / Q000032:analysis; D012702:Serotonin Antagonists / Q000378:metabolism* / Q000494:pharmacology
D000662:Amphetamines; D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D017374:Paroxetine; D015104:3,4-Methylenedioxyamphetamine; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine