Radioactive N,N‐Dimethylphenylethylamine: A Selective Radiotracer for In Vivo Measurement of Monoamine Oxidase‐B Activity in the Brain

Abstract

N-[methyl-14C]N,N-dimethyphenylethylamine (DMPEA) was synthesized and its availability as a selective radiotracer for in vivo measurement of mouse brain monoamine oxidase (MAO) activity was examined. Relatively high incorporation of labeled DMPEA into brain (.apprx. 10% of the injected dose/g of brain) was observed just after its injection. Radioactive dimethylamine, a metabolite produced from labeled DMPEA in the brain 1 h after DMPEA injection, was reduced in a dose-dependent manner by pretreatment with various doses of a specific MAO-B inhibitor, 1-deprenyl, but was not reduced appreciably by pretreatment with a specific MAO-A inhibitor, clorgyline. Pretreatment with 1-deprenyl did not affect significantly the rate of incorporation of the radiotracer DMPEA into the brain, suggesting that reduction of the radioactivity in brain by this compound might be due to a decrease in the rate of production of the radioactive metabolite dimethylamine by brain MAO-B. The amount of the radioactive metabolite trapped in the brain was proportional to the brain MAO-B activity remaining afrer pretreatment with 1-deprenyl. In vitro deamination of DMPEA by mouse brain MAO showed a higher sensitivity to inhibition by 1-deprenyl than that by clorgyline. Evidently, DMPEA is a selective substrate for mouse brain MAO-B both in vivo and in vitro, and the positron emitter [11C]DMPEA might be used instead of [14C]DMPEA as a radiotracer for in vivo measurement of MAO-B activity in human brain.