Recent positron emission tomography imaging studies have demonstrated a significantdecrease in both monoamine oxidase A and B (MAO-A and MAO-B) activities in the brains ofsmokers. Normal levels of activity are observed in former smokers, suggesting the presence ofone or more compounds in
tobacco smoke that may inhibit these enzymes. In this paper, wereport the results of efforts to identify compounds present in
flue-
cured tobacco leaves thatinhibit MAO. The isolation procedure was guided by estimating the inhibitory properties of
tobacco leaf extracts on the liver mitochondrial MAO-B-catalyzed oxidation of 1-methyl-4-(1-methylpyrrol-2-yl)-1,2,3,6-tetrahydropyridine to the corresponding dihydropyridinium metabolite. Fractionation of extracts from
flue-
cured tobacco leaves led to the isolation of a competitiveinhibitor of human MAO-A (
Ki = 3
![](/images/entities/mgr.gif)
M) and MAO-B (
Ki = 6
![](/images/entities/mgr.gif)
M), the structure of which couldbe assigned by classical spectroscopic analysis and confirmed by synthesis. This informationmay help to provide insights into some aspects of the pharmacology and toxicology of
tobaccoproducts.