New Schizophrenia Drugs Will Target Glutamate
> 2/25/2008 2:34:10 PM

While antipsychotics can greatly improve the lives of people with schizophrenia, the side effects that often accompany these medications can complicate treatment. Faced with serious symptoms like weight gain, facial tics, and shaking, many patients stop taking their medication. Yesterday's New York Times highlighted recent efforts by scientists to develop medications that will effectively alleviate the symptoms of schizophrenia without causing serious side effects. By using a new technique—targeting glutamate rather than dopamine— these researchers may have identified a new and well-tolerated medication for schizophrenia.

The first antipsychotics, which were the developed in the 1950s, blocked dopamine receptors in the brain, and every antipsychotic developed since then has worked in much the same way. But, in the 1980s, researchers discovered that the illicit drug PCP, which causes symptoms closely resembling those of schizophrenia, blocks the glutamate receptor NMDA, and they soon began to study glutamate's involvement in schizophrenia. They found that some receptors activated by glutamate, called "metabotropic,"moderated the amount of glutamate released by the cells, and researchers began developing drugs that would selectively target these receptors.

The innovative work of one scientist in particular, Dr. Darryle Schoepp, was well-received last September. Published in Nature Medicine, his study tested the Eli Lilly drug currently known as LY2140023. Among nearly 200 subjects, this drug was only slightly less effective than current antipsychotics and had fewer adverse symptoms. In addition, this drug improved the symptoms of schizophrenia that other antipsychotics don't help—cognitive problems and "negative" symptoms (social withdrawal, loss of interest in daily activities). That study was preliminary, and Eli Lilly has already begun a second study of LY2140023 that will include 870 patients and is set to be completed in January 2009. If the results of this study support the previous findings, Eli Lilly plans to test the drug in a trial of thousands, and federal approval of the drug, if it proves to be effective, may only be a few years away.

Other drug companies have also begun developing drugs that target glutamate, investigating the role glutamate might play in schizophrenia and other disorders, and these studies may yield new advancements. By approaching the issue of schizophrenia medication from a new angle, researchers may be able to offer new treatment options to those struggling with this debilitating disorder.

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