STUDIES ON THE INTERACTION BETWEEN 1,2,3,4-TETRAHYDRO-BETA-CARBOLINE AND CIGARETTE-SMOKE - A POTENTIAL MECHANISM OF NEUROPROTECTION FOR PARKINSONS-DISEASE

1,2,3,4-Tetrahydro-beta-carboline (TH beta C) is an endogenous or envi ronmental neurotoxic factor putatively involved in the development of Parkinson's disease (PD). As part of our efforts to characterize the m echanism of the reported protection of smoking against PD, we have exa mined the interaction between TH beta C and cigarette smoke. We found that TH beta C reacts in vitro and under physiological conditions with some components of cigarette smoke to form N-2-(cyanomethyl)-TH beta C (CM-TH beta C), N-2-(1'-cyanoethyl)-TH beta C (CE-TH beta C), N-2-(1 '-cyanopropyl)-TH beta C (CP-TH beta C), N-2-(1'-cyanobutyl)-TH beta C (CB-TH beta C) and N-2-formyl-TH beta C (F-TH beta C). Significant di fferences in the recovery of some of these TH beta C-derivatives were obtained for Burley and Bright tobacco. Several of the reported compou nds showed reversible and competitive MAO-A inhibitory properties. The detection of some of these compounds in rat brain after chronic admin istration of TH beta C and a solution of cigarette smoke proved that t he reported interactions also occur in vivo. These results are discuss ed as a potential mechanism of neuroprotection in the development of P D. (C) 1998 Elsevier Science B.V. All rights reserved.