DefinePK

Abstract

Break the Cigarette


As with most addictions, smoking and tobacco addictions are immensely challenging behaviours to change. For years, various pharmacological and non-pharmacological methods to reduce and discontinue smoking have been tried, with limited success. Recently, Johnson and Stout published a remarkable study in Nature Structural and Molecular Biology on the pharmacology of a drug called Methoxsalen. 1 This drug has been clinically proven to decrease smoking. The mechanism of action proposed in this study is that methoxsalen interacts with and blocks the action of cytochrome P450 2A6 which degrades nicotine. The binding pattern and specific action is detailed in the study. Cytochrome P450 2A6 also breaks down carcinogens found in tobacco to more harmful chemicals that can cause cancer. People who have nicotine addiction continue to smoke to maintain high nicotine levels in the brain. By preventing nicotine breakdown Methoxalen could help people reduce their craving for nicotine and stop smoking. Understanding this drug interaction will help guide future studies aimed at improving inhibitor design. Ultimately, this may lead to better drugs aimed at decreasing nicotine dependence that at the same time could also reduce the risk of tobacco-related cancers. 1. Yano JK, Hsu MH, Griffin KJ, Stout CD, Johnson EF. Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. Nat Struct Mol Biol 2005;12:822-3.