Mecamylamine blocks the action of nicotine, and potentially cocaine, by lowering the net amount of dopamine available in the brain. While cocaine still boosts available levels of dopamine, its overall amount is decreased because mecamylamine has plugged up some of the nicotinic receptor sites where the brain would naturally be activating its own dopamine.

"In other words, the brain has its own chemical, acetylcholine, that stimulates the release of dopamine. Mecamylamine comes along and occupies some of the nicotinic acetylcholine receptor sites and prevents them from activating dopamine," Rose said. "So the net effect is that less dopamine is being produced, even when cocaine comes along and boosts dopamine levels through a different pathway."

Rose said the person still desires nicotine or cocaine, but the desire is weakened because the brain is no longer being flooded with dopamine.

"Mecamylamine reduces desire, but it doesn't quench it," he said. "Yet given how few medications there are to combat serious addictions, even a medication that reduces craving can be of significant benefit."

Already, mecamylamine has proven to be of significant benefit in helping people quit smoking. In earlier Duke studies, Rose demonstrated that using a patch with nicotine and mecamylamine together helped 40 percent of smokers quit for at least one year, while only 15 percent of smokers were able to do so using the patch alone.

The researchers expect mecamylamine to be approved for smoking cessation sometime this year.

Co-authors of the Duke study include Rose, Tonya Mead, Amir Rezvani, Camille Gallivan and Rita Gross.

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Contact: Renee Twombly
Twomb001@mc.duke.edu
919-684-4148
Duke University Medical Center
7-Apr-2000