The University of Illinois at Chicago has received a five-year, $4.8 million federal grant to develop new therapeutics to treat depression.

Depression, a serious medical illness involving the brain, affects more than 20 million people in the United States, according to the National Institute of Mental Health. Symptoms can include sadness, loss of interest in activities that were once enjoyed, weight change, difficulty in sleeping (or oversleeping), loss of energy, feelings of worthlessness and thoughts of death or suicide.

The illness can run in families, and it occurs more often in women than men. The most common treatment option is the combination of antidepressant medication and psychotherapy. Other treatments include lifestyle, behavioral and thought modifications, and alternative and complimentary medicines.

What’s needed are antidepressants that work faster, have fewer side effects and that act pharmacologically in new ways, says Alan Kozikowski, UIC professor of medicinal chemistry and pharmacogonosy and the grant’s principal investigator.

Kozikowski and his research team had been designing and synthesizing novel nicotine-like compounds that target certain receptors in the brain, in hopes that they would improve cognition in Alzheimer’s disease. Studies in animal models revealed that some of these compounds had antidepressant activity.

“We thus chose to focus our program on depression, as this offered a very different target that might lead to something better, with a faster onset of action,” Kozikowski said.

While the main focus of the research now is to develop medications for depression, Kozikowski said it’s likely some candidate compounds may have other clinical applications, including the treatment of schizophrenia, pain and nicotine dependence.

In fact, the UIC drug discovery group - which also includes investigators from the Barrow Neurological Institute in Phoenix and from PsychoGenics Inc. in Tarrytown, N.Y. - has already found that some of these novel agents do work for pain in animal models.

Prior research has also shown that many smokers smoke to improve their mood, supporting the notion that nicotine itself has antidepressant properties. This would explain, Kozikowski said, why cigarette smoking is much more common among depressed individuals. A recent study found that smokers are 41 percent more likely than nonsmokers to suffer from depression.

Such studies suggest that nicotinic compounds that have been modified to reduce their addictive potential while retaining the ability to balance mood could provide a new family of antidepressant drugs, he said.

This new drug class could have greater efficacy and fewer side effects than antidepressant medications currently on the market that work by inhibiting monoamine reuptake, Kozikowski said. Side effects of current antidepressants include headache, nausea, insomnia, dry mouth, constipation and agitation.

In spite of the intensive efforts that have gone into the design and study of nicotinic drugs, very few of the compounds have reached clinical trials, Kozikowski said.

The new grant is part of the National Cooperative for Drug Discovery and Development Groups and is funded by the National Institute of Mental Health, one of the National Institutes of Health.

Kozikowski’s coworkers include Rong He, research assistant professor at UIC; Andrew Mesecar, professor in the UIC Center for Pharmaceutical Biotechnology; Jianhua Liu, postdoctoral research associate at UIC; Ron Lukas, of the Barrow Neurological Institute; and Barbara Caldarone of PsychoGenics Inc.

For more information about UIC, visit http://www.uic.edu.

Released: 8/18/2009 1:30 PM EDT
Source: University of Illinois at Chicago