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Drug in Development Targeting Nicotine Metabolism

Hand holding cigarette (NIMH)

(National Institute of Mental Health)

Research underway at the Academy of Finland in Helsinki is developing a new type of drug that could help smokers quit the habit. The new drug would slow down the metabolism of nicotine, which would help reduce the addictive power of their smoking.

Nicotine is absorbed quickly through the lungs and the lining of the mouth, from where it passes through the body and into the brain. Once nicotine reaches the liver, it is metabolized by an enzyme called CYP2A6. Preliminary studies by the Canadian partner in the project have shown that inhibitors of the nicotine-metabolizing CYP2A6 enzyme can help smokers curb the need to smoke.

Current CYP2A6 inhibitors, however, are not real options for anti-smoking therapy, since they have too many adverse side effects. The Academy of Finland team, headed by Hannu Raunio, professor of pharmacology at the University of Eastern Finland, is developing a more targeted CYP2A6 inhibitor that would only be effective in specific parts of the body.

Raunio’s team so far has developed a clear picture of the structure of CYP2A6 that will enable them to use computer-aided modeling to design molecules that bind specifically to their targets without disturbing other functions in the body. At this point, four years into the project, Raunio’s team has discovered several molecules in CYP2A6’s structure, and gained insights into how the molecules bind to the center of the enzyme.

More work and resources are still needed to develop a drug available to the public, Raunio notes. Rather than preventing or relieving withdrawal symptoms — the strategy of many current therapies for smoking addiction — this drug aims to reduce the impact of nicotine on the brain and body, causing the addiction itself.

Read more: Panel: Make Cigarettes Non-Addictive

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