Drugs and genotypes: how pharmacogenetic information could improve smoking cessation treatment.
Current smoking cessation treatments are not optimal as the long-term abstinence rates are low. Nicotine replacement therapy and bupropion are the only pharmacotherapies widely available to smokers and there is a need to improve current cessation treatments and to develop new drug therapies. Our goal is to use pharmacogenetic information to improve smoking cessation treatments. Candidate genes include those involved in central mechanisms (such as genes encoding the nicotinic acetylcholine receptors, dopamine receptors, dopamine transporters and opioid receptors) and peripheral mechanisms (such as genes encoding the drug-metabolizing enzymes CYP2A6 and CYP2B6). Pharmacogenetics could be used to improve current smoking cessation treatments through two general approaches. The first would be to identify novel drug targets based on genetic variants that are associated with a natural protection against nicotine dependence, decreased smoking behaviour and/or increased smoking cessation. This knowledge could be used to develop drugs that can mimic these advantages, reducing the risk for acquisition, block the rewarding effects of smoking, decreasing the amount smoked and increasing cessation. The second would be to identify smokers with particular genetic variants who are likely to respond better to one treatment (or dose) versus another and to individualize their treatment to maximize long-term abstinence. This review will highlight examples of how pharmacogenetic information from central and peripheral candidate genes could contribute to improving smoking cessation outcomes by these two approaches.
Lee
Anna M
AM
Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, Canada.
Tyndale
Rachel F
RF
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D004358:Drug Therapy / Q000379:methods*; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism; D016540:Smoking Cessation / Q000379:methods
D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; D011978:Receptors, Nicotinic; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6