LOS ANGELES--By targeting the enzyme that metabolizes nicotine, researchers at the University of Toronto have devised a new strategy to wean smokers from cigarettes.
"This principal is quite different than anything currently in use," said Edward M. Sellers, MD, lead investigator of a study presented during the annual meeting of the American Society for Clinical Pharmacology and Therapeutics. The presentation is part of a panel describing new findings in the metabolic aspects of smoking and drug abuse.
Sellers' research has focused on the cytochrome P450 2A6 enzyme, which metabolizes nicotine to its inactive byproduct cotinine and activates carcinogens in tobacco smoke. By inhibiting the action of the enzyme, more nicotine remains in the bloodstream and the pleasure smokers get from a cigarette lasts longer. As a result, smokers may light up less frequently. Blocking the enzyme also prevents activation of carcinogenic substances in tobacco smoke.
"Smoking is a regulated behavior," Sellers said. "People will not let their nicotine levels go beyond a certain amount. If they go up momentarily, smokers will take fewer or smaller puffs. That can be the first step to quitting." Most current smoking cessation methods reduce withdrawal symptoms by replacing nicotine via patches, gum, inhalers or vaporizers. The prescription drug Zyban is an anti-depressant approved for use as a stop-smoking aid.
In a study with 11 smokers, Sellers has demonstrated that the psoriasis drug methoxsalen is a potent enzyme inhibitor, capable of increasing blood levels of nicotine while reducing exhaled carbon monoxide. Little of the drug enters the bloodstream, reducing exposure to internal organs and other body tissue. Sellers cautions, however, that methoxsalen has not been approved for use in smoking cessation. More safety testing is needed, but the concept is very promising.
"In this research we know that if we inhibit the enzyme, if we find a new drug that does that, the concept will work," Sellers said.
Founded in 1900, the ASCPT consists of over 2200 professionals whose primary interest is to promote and advance the science of human pharmacology and therapeutics. The Society is the largest scientific and professional organization serving the discipline of Clinical Pharmacology.
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