Decreasing smoking behaviour and risk through CYP2A6 inhibition.
The consequences of tobacco dependence are both health related and economic. Novel treatment approaches are needed to offer alternatives to patients and to improve treatment outcomes. We review concepts and selected recent discoveries in the area of treatment, with a specific orientation towards drug development. Current treatments are outlined and we highlight new strategies that are based on the manipulation of cytochrome P450 2A6 (CYP2A6) activity, which is responsible for the metabolism of nicotine. The clinical implications of CYP2A6 polymorphisms have been linked to a decreased risk of tobacco dependence, a decrease in number of cigarettes smoked and reduced risk of tobacco-related cancers. Further, we discuss a range of models for proof-of-concept studies for new treatments to alleviate tobacco dependence
Sellers
Edward M
EM
Department of Pharmacology, Psychiatry, Medicine University of Toronto, Ontario M5T 3A9, Toronto, Canada. e.sellers@ventana-crc.com
Tyndale
Rachel F
RF
Fernandes
Leona C
LC
D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors* / Q000235:genetics; D065637:Cytochrome P-450 CYP2A6; D006801:Humans; D008730:Methoxsalen / Q000627:therapeutic use; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors* / Q000235:genetics; D009538:Nicotine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D015995:Prevalence; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000201:enzymology / Q000453:epidemiology
D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D008730:Methoxsalen