Studies on the interaction between 1,2,3,4-tetrahydro-β-carboline and cigarette smoke: a potential mechanism of neuroprotection for Parkinson's disease

• Published in: Brain research 1998-08, Vol.802 (1), p.155-162
• Main Authors: Soto-Otero, Ramón, Méndez-Álvarez, Estefanı́a, Riguera-Vega, Ricardo, Quiñoá-Cabana, Emilio, Sánchez-Sellero, Inés, López-Rivadulla Lamas, Manuel
• Format: Article
• Language: English
• Subjects: 1,2,3,4-Tetrahydro-β-carboline; Animals; Biological and medical sciences; Brain - enzymology; Carbolines - analysis; Carbolines - chemistry; Carbolines - pharmacology; Cigarette smoke; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopaminergic neuroprotection; Drug Interactions; Gas Chromatography-Mass Spectrometry; Humans; Male; MAO inhibition; Medical sciences; Monoamine Oxidase Inhibitors - pharmacology; Neurology; Neuroprotective Agents - pharmacology; Nicotiana; Parkinson Disease - prevention & control; Parkinson's disease; Plants, Toxic; Rats; Rats, Sprague-Dawley; Smoke; Solutions - chemistry; Solutions - pharmacology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(98)00538-1

1,2,3,4-Tetrahydro-β-carboline (THβC) is an endogenous or environmental neurotoxic factor putatively involved in the development of Parkinson's disease (PD). As part of our efforts to characterize the mechanism of the reported protection of smoking against PD, we have examined the interaction between THβC and cigarette smoke. We found that THβC reacts in vitro and under physiological conditions with some components of cigarette smoke to form N 2-(cyanomethyl)-THβC (CM-THβC), N 2-(1′-cyanoethyl)-THβC (CE-THβC), N 2-(1′-cyanopropyl)-THβC (CP-THβC), N 2-(1′-cyanobutyl)-THβC (CB-THβC) and N 2-formyl-THβC (F-THβC). Significant differences in the recovery of some of these THβC-derivatives were obtained for Burley and Bright tobacco. Several of the reported compounds showed reversible and competitive MAO-A inhibitory properties. The detection of some of these compounds in rat brain after chronic administration of THβC and a solution of cigarette smoke proved that the reported interactions also occur in vivo. These results are discussed as a potential mechanism of neuroprotection in the development of PD.