Effects of d-methamphetamine on monkey brain monoamine oxidase, in vivo and in vitro.
A and B form MAO activities in mitochondria and synaptosome were measured in the brain of monkeys administered d-methamphetamine (d-MP) 2 mg/kg, i.m., daily for 7 days. When mitochondria were used as an enzyme preparation, the Km and Vmax values decreased with 5-HT (serotonin for A-form MAO substrate) and beta-phenylethylamine (beta-PEA for B-form MAO substrate), while in the synaptosome, a significant increase of the Km and Vmax values was observed with 5-HT and dopamine as substrates. The mitochondrial MAO treated with d-MP was inhibited strongly by clorgyline and deprenyl with beta-PEA as a substrate, while synaptosomal MAO was highly sensitive to these MAO inhibitors with 5-HT as a substrate. MP and amphetamine (AP) were found in brain mitochondrial and synaptosomal preparations of monkeys administered 2 mg/kg d-MP, i.m. daily for 7 days; MP and AP contents were 5.05 +/- 0.22 pg/mg protein and 37.3 +/- 3.8 ng/mg protein in mitochondria and 2.35 +/- 0.35 pg/mg protein and 46.4 +/- 1.5 ng/mg protein in synaptosomes, respectively. MAO was inhibited by MP and its metabolites, AP p-hydroxymethamphetamine (OH-MP) and p-hydroxyamphetamine (OH-AP), with 5-HT, beta-PEA and dopamine as substrates, in vitro. MP and its metabolites were more potent inhibitors of A-form MAO than B-form MAO.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003010:Clorgyline / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D008694:Methamphetamine / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism*; D012642:Selegiline / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D012642:Selegiline; D008694:Methamphetamine; D008995:Monoamine Oxidase; D003010:Clorgyline; D003913:Dextroamphetamine