Inhibition of brain monoamine oxidase by adducts of 1,2,3,4-tetrahydroisoquinoline with components of cigarette smoke

Abstract

A series of adducts of 1,2,3,4-tetrahydroisoquinoline (TIQ) and some components of tobacco smoke were investigated for their ability to inhibit rat brain monoamine oxidase. 1-Cyano-TIQ (1CTIQ), N-(1'-cyanoethyl)-TIQ (CETIQ), N-(1'-cyanopropyl)-TIQ (CPTIQ), and N-(1'-cyanobutyl)-TIQ (CBTIQ) were found to act as competitive inhibitors for both MAO-A and MAO-B. Ki values ranged from 16.4 to 37.6 microM. N-(Cyanomethyl)-TIQ (CMTIQ) was not found to be an inhibitor (Ki > 100 microM). These findings may help to explain the in vivo inhibitory effects of tobacco smoke on MAO activity and the suggested protective effect of tobacco smoking against Parkinson's disease. They also appear to reinforce the usefulness of reversible MAO inhibitors in smoking cessation and abstinence. However, different results must be expected between Burley and Bright tobacco.