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October 2000
Vol. 3, No. 8, p. 21.

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A step to freedom from smoking?

Through the inhibition of an enzyme involved in nicotine metabolism, a research group has been able to change the smoking habits of tobacco-dependent subjects.

In earlier studies, Edward Sellers and colleagues at the Sunnybrook and Women’s College Health Sciences Centre (Toronto) noted that individuals with mutations that inactivate CYP2A6, a gene encoding a cytochrome P-450, were less likely to become addicted to nicotine.

The Toronto researchers believed that by inhibiting CYP2A6, blood nicotine levels would be maintained and smokers would be less likely to light up. They tested this theory by administering the CYP2A6 inhibitor methoxsalen or a placebo as well as orally administered nicotine or placebo to several subjects who smoked and had no interest in quitting. They then followed the maintenance of blood nicotine levels and observed the behavior of the subjects while they smoked after a period of abstinence (Clin. Pharmacol. Ther. 2000, 68, 35–43).
Inhibiting CYP2A6 with methoxsalen. Researchers hope to slow the conversion of nicotine to cotinine and thus alter the habits of smokers.

Blood nicotine levels were highest in subjects who received the inhibitor and nicotine, followed by those who received only the inhibitor. This result was mimicked behaviorally as subjects receiving both the inhibitor and nicotine smoked 24% fewer cigarettes, inhaled less deeply, and had longer lag times between cigarettes than those receiving only placebos.

The researchers believe that their findings prove the efficacy of CYP2A6 inhibition in conjunction with oral nicotine administration (nicotine gum) as a method of reducing smoking.


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