Experimental drug curbs smokers' nicotine cravings

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An experimental drug that blocks certain brain receptors can reduce nicotine cravings in addicted rats and baboons - a finding researchers say could lead to new medicines to help people stop smoking for good.

The candidate drug, called GSK598809, belongs to a class of compounds that block a specific type of dopamine receptor in key areas of the brain linked to tobacco addiction.

It is now ready for testing in early-stage clinical trials in humans, said Manolo Mugnaini, a researcher at the Aptuit Centre for Drug Discovery and Development in Verona, Italy, which was formerly owned by GlaxoSmithKline.

The drug was originally being developed by GSK, but the British drugmaker decided in 2010 to end investment in some areas of neuroscience research, and halted work on GSK598809 as part of that decision. The compound is now part of a research project using imaging scans to explore brain mechanisms behind impulsivity, stress and addiction.

Previous studies have shown that nicotine in tobacco smoke increases the release of the brain chemical dopamine in the ventral striatum, midbrain and pallidum - all parts of the brain thought to play a key role in getting smokers hooked.

The World Health Organisation says there are a billion smokers worldwide and tobacco kills up to half of its users.

Cravings reduced

Mugnaini said the animal tests as well as some very early studies in humans suggested GSK598809 blocks dopamine receptors in the brain known as D3 receptors, and helps reduce cravings.

"This is the first time with this class of drugs that we have had signals of efficacy in humans," he told Reuters.

"And what is more important about this work is that we have provided a method that can be used to take this class of compounds from pre-clinical trials to full human trials."

He said brain imaging was key to that future development.

"From our study we have pictures of the drug going to the right expected target, the D3 subtype of dopamine receptors, in brain areas that play a key role in nicotine addiction in the brain," he said.

"By following this model based on imaging of the brain, we know we can monitor the performance of the drug in humans in an efficacious way."

Mugnaini and colleagues tested GSK598809 on rats and baboons and used data from those experiments to create a model to find an appropriate dose level for humans. They then treated smokers who agreed to go without cigarettes overnight with GSK598809 and found that it partially alleviated their nicotine cravings.

More importantly, Mugnaini said, the brain imaging studies suggested that higher doses of GSK598809 than those used in the human tests may be more effective at reducing smokers' cravings.

The study's findings were published in the journal Neuropsychopharmacology on Wednesday.

Several drugs are already on the market to help smokers quit, including Pfizer's Chantix or Champix, and GSK's Zyban, an antidepressant also approved for smoking cessation.

Although there are years of testing ahead before this experimental drug may be licensed for use in patients, Mugnaini said it could one day be used alongside a drug like Chantix.

Because they have different modes of action, Chantix may be more beneficial in helping smokers take the initial step of quitting, he said, while a new drug from GSK598809's class would be designed to reduce cravings once they have stopped, limiting the risk they will relapse, a common problem for smokers.

The American Lung Association (ALA) estimates it takes the average smoker five or six serious attempts to finally quit.