Part 2 of 2
Part 1: The Risks of Quitting Smoking

Wendy Wolfson
Newswire21.org

There's substantial proof that Chantix, Pfizer's new antismoking drug, can help people who have a hard time giving up cigarettes more than a competing pill or placebos.

In six clinical trials involving 3,659 smokers, an average of 29 percent of people quit smoking for a year, compared to 23 percent for smokers taking Zyban and 12 percent of the people getting sugar pills, according to data reported by Pfizer.

Annual smoking-related deaths. (CDC)

The question is why it works, and what triggers rare side effects that range from nausea to suicide (See: Part 1: The Risks of Quitting Smoking).  The answer reflects some still-evolving research into addictions and other, more serious psychiatric problems.

Chantix was the first drug on the market from a new class of pharmaceuticals that target neural nicotinic receptors, or NNRs. The receptors help signal the brain, the central nervous system and skeletal muscles.

NNRs are like knobs that can dial up or down the flow of chemicals like acetylcholine and dopamine that influence mood, memory and cognition.

As almost everyone knows by now, cigarettes contain the highly addictive drug nicotine along with about 3,800 other chemicals. They are connected to hundreds of thousands of deaths each year in the US alone. Nicotine molecules activate the NNRs, which is why a cigarette can focus your attention or calm your nerves, and what makes it harder to quit smoking. 

But nicotine also has a virtuous side. In recent years, scientists started realizing that nicotine can be beneficial when divorced from its unsavory companions. For example, nicotine seems to have a protective effect against Parkinson's disease and Alzheimer's disease, though not vascular dementia.

In a number of small studies, researchers even put nicotine patches on people with the kind of  mild cognitive impairment associated with impending Alzheimer's disease and saw modest improvements.

The problem with delivering nicotine directly, say, through patches, is that the NNRs develop tolerance, according to Marina Picciotto, a psychiatry professor at Yale University Medical School, who received funding from Pfizer to study depression among people taking Chantix.

New Direction
So, during the 1990's, researchers started developing drugs for conditions where the NNRs go haywire, targeting different receptors for conditions such as major depression, cognitive problems associated with schizophrenia, Alzheimers disease, ADHD, Parkinson's disease and, of course, smoking. Chantix is the first NNR drug to come to market.

"They normalize the neurotransmitter tone in the brain," according to Dr. Merouane Bencherif, VP of Preclinical Research at Targacept, a N.C.-based biotech firm that was spun out of the research division of R.J. Reynolds, the tobacco company that makes Camels, Kool and Winston cigarettes.

Chantix, for example, works by preventing nicotine from activating certain receptors and stimulating the "reward" your brain feels with a nicotine rush.

"The end result is that you are perhaps preventing the negative consequences of nicotine withdrawal from smoking, for example, by replacing that nicotine a little bit. But you are also preventing the full effect of nicotine if you smoke on top of it," said Picciotto.    

People with a history of serious psychiatric illness were excluded from the clinical trials for Chantix with the goal of minimizing the influence of unrelated factors. According to Dr. Marina Brodsky, a Medical Team Leader at Pfizer, all new medicines not specifically intended for psychiatric problems are first studied in patients without serious, active medical or psychiatric problems, with the goal of minimizing any impact on the study.

Psychiatric Study
"Pfiizer is continuing to conduct clinical research in multiple populations, including patients with a history of psychiatric disorders,"  Brodsky told Newswire21.

To be sure, fine-tuning dosage and delivery is always an issue with new drugs. So is selectivity. Nicotinic drugs need to precisely target or block the right receptor groups to avoid side effects which, in the case of Chantix, can range from nausea to suicidal thoughts in small numbers of users.

"Current nicotinic drugs are not very selective." said Dr. Daniel Timmerman, VP of Pharmacology at Danish biotech Neurosearch, which has an NNR drug program.

According to Brodsky, Chantix is very selective for a certain type of nicotinic receptor "...and at therapeutic levels, does not bind to other neurotransmitter receptors and transporters, including those implicated in mental disorders."

But genetic studies to determine who will and won't respond to NNR drugs are in their infancy.

In the meantime, if you are taking any kind of anti-smoking medication, read the label. The FDA says to report any mood changes promptly to your doctor.