The Upside to Nicotine?

New drugs that target the brain's nicotine receptors, without the addictiveness of cigarettes, might help memory impairment in Alzheimer's disease and schizophrenia.

Could drugs that mimic nicotine help boost brain power? Several companies and academic research groups are banking on it, with a handful of compounds showing promising results in preliminary human tests.

Nicotine, even without the carcinogenic effects of smoking, has major downsides: it's addictive and can increase heart rate and blood pressure. But now scientists are trying to develop drugs that target the brain's nicotine receptors to treat an array of cognitive impairments without these side effects. Several candidates are now being tested or about to be tested in clinical trials to treat Alzheimer's disease, schizophrenia, and age-related memory loss.

"Everyone knows that smoking does good things and bad," says David Lowe, chief scientific officer at Memory Pharmaceuticals, a biopharmaceutical company based in Montvale, NJ. "We're trying to focus on receptors that mediate the good things."

The good things include a positive effect on memory and attention, as evidenced both by cognitive testing and by the legions who file outside for smoke breaks before an exam or an important meeting. Meanwhile, smokers have a lower risk of developing Parkinson's and possibly Alzheimer's diseases. And people with schizophrenia and attention deficit disorder are much more likely to smoke than the general population; scientists believe that these patients may be unconsciously self-medicating to make up for some kind of deficit in the brain.

Several companies hope to turn these observations into therapies. Targacept, a drug development company based in North Carolina, has developed a compound that targets a specific type of nicotine receptor known as the alpha-4/beta-2 receptor. In a study of almost 200 people, both patients with age-related memory problems and healthy controls, researchers found that those who had taken the drug performed significantly better on tests of memory and attention. The company is now planning a larger trial of approximately 1,400 people, in collaboration with pharmaceutical manufacturer AstraZeneca, to determine whether the drug can improve cognitive problems in both Alzheimer's disease and schizophrenia. Pharmaceutical giant Abbott is testing similar compounds in Alzheimer's disease, schizophrenia, and ADHD.

Memory Pharmaceuticals is targeting a different type of nicotine receptor, known as the alpha-7 receptor. Preliminary studies in healthy volunteers showed that the compound could improve some types of memory. And a similar compound, developed at the University of Florida, has shown success in a small trial against the memory and attention problems that make it difficult for many people with schizophrenia to work and have meaningful relationships. (Schizophrenia medications currently on the market treat only the hallucinations and delusions that characterize the disease.) Like Targacept, Memory Pharmaceuticals plans to test its compounds in both Alzheimer's and schizophrenia patients.