Is tobacco about to meet its match?
New insights into how nicotine behaves in the body are paving the way for better drugs to help smokers beat their addiction, researchers reported this week at the American Association of Pharmaceutical Scientists' annual meeting in Baltimore.
According to the Centers for Disease Control and Prevention, 70 percent of the nation's 46 million smokers say they want to quit. But fewer than 5 percent of those who go cold turkey manage to stay nicotine-free. Most last less than a week.
Smokers who turn to cessation aids, including behavioral therapy and drugs such as Zyban or nicotine gums and patches, fare better - but not by much. Fewer than 25 percent of smokers who use cessation aids are tobacco-free after one year. One result: 440,000 Americans wind up dying from smoking-related causes annually.
"There's certainly a need for novel medications," says Tony George, a Yale University psychiatrist who studies and treats nicotine addicts.
One of the more promising experimental drugs being tested in humans is Varenicline. Developed by Pfizer, the drug is the first anti-smoking therapy specifically designed to target the brain's nicotine receptors.
Each time a smoker takes a drag, nicotine travels through the lungs and into the bloodstream. Seconds later, it's in the brain. There it latches onto a complex receptor known as the nicotinic acetylcholine receptor, or nACh, which triggers the release of the chemical dopamine.
Dopamine is the body's ubiquitous feel-good drug. "Anything you find pleasurable releases dopamine - rock and roll, food, sex, what have you," says Linda Dwoskin, a nicotine researcher at the University of Kentucky.
So each puff on a cigarette triggers a blissful dopamine jolt. But as dopamine levels drop off, it leads to the potent cravings that force most smokers to pull out their packs. "This happens with every hit of the cigarette you take," says Jotham Coe, a Pfizer chemist who helped develop Varenicline.
But the question remained: What to do with this molecular machinery?
Pfizer researchers concluded that bottling up the nACh receptors or activating them, as the nicotine patch does, wouldn't work. Both could actually motivate smokers to suck up even more nicotine.
Then Pfizer researchers heard about an anti-smoking compound studied by Soviet scientists in the 1970s. The substance, called cytisine, partially blocked nicotine receptors.
