Nicotine Holds Key to More Effective Painkillers

April 29, 1999 NY Times 
By REUTERS LONDON

French scientists have discovered how nicotine works in the brain to ease pain, which could pave the way for new drugs that are more effective but less addictive than morphine, they said Wednesday. Nicotine, the addictive element in cigarettes, dulls pain by interacting with certain receptor molecules in the brain. Scientists have isolated and cloned 10 nicotine receptors but until now they had not known which receptors were responsible for nicotine's varied behavioral effects.

Jean-Pierre Changeux and a team of scientists at the Molecular Neurobiology Unit at the Institute Pasteur in Paris bred a strain of mice lacking the gene for the alpha-4 and beta-2 receptors. Their research is published in the latest edition of the science journal Nature. "We found that both of these receptors, the alpha-4 and beta-2, play a large role in mediating the effects of nicotine," Lisa Marubio, one of the researchers, said in a telephone interview.

Nicotine itself cannot be used as an analgesic because of its addictive properties and toxic effects on the heart and lungs. But its pain receptors could be targets for a new class of powerful painkillers. "Compounds that are similar to nicotine that can be synthesized in a lab can possibly be used as potential new analgesics that can be every bit, if not more, efficacious than morphine," said Marubio. The researchers tested the reaction of normal mice and mice lacking the alpha-4 and beta-2 receptors to pain. Without nicotine, the second group of mice behaved just like the normal mice. But when they were exposed to nicotine they did not experience its analgesic effects and felt the pain. "These receptor subunits are an important, although not exclusive, component of the nicotine pain pathways," the researchers said in Nature report.

Scientists already have started looking at nicotine and nicotine-like compounds as a new class of painkiller. The French results could speed up the search. "Specific pharmacological compounds that target these receptors may prove to be therapeutically useful for analgesia," the researchers added.