New Target for Anti-Anxiety Drugs Identified

[Max]

New Target for Anti-Anxiety Drugs Identified
Wed Oct 2,10:45 AM ET
By Merritt McKinney

NEW YORK (Reuters Health) - By studying a type of mouse that is more daring and less prone to anxiety and stress than its peers, California researchers have identified an enzyme that may be a good target for anti-anxiety drugs.



The hope is that blocking the enzyme may relieve anxiety symptoms without causing a person to feel sedated, according to the study's lead author, Dr. Robert O. Messing from the University of California, San Francisco's Ernest Gallo Clinic and Research Center in Emeryville.

Many anti-anxiety drugs work by targeting a substance in the central nervous system called gamma aminobutyric acid (GABA). While these drugs, which stimulate a receptor called GABA-A, can control anxiety symptoms, they can be addictive as well as cause people to feel sluggish and sedated.

Messing and his colleagues previously found that mice lacking an enzyme called PKCe are especially sensitive to drugs that bind to GABA-A, so they wondered whether the absence of this enzyme would have anti-anxiety effects in mice.

Writing in the October issue of the Journal of Clinical Investigation, Messing's team reports that mice that lack PKCe were less anxious and showed less stress than other mice. They were more likely to venture into open areas--an anxiety-producing situation for mice--and had produced fewer stress hormones when enclosed in a small space for a short period of time.

These mice were especially sensitive to natural calming steroids found in the brain. But when the mice were given a drug that blocked the GABA-A receptor, anxiety-like behavior and stress hormones increased. This suggests that drugs that block PKCe might reduce anxiety, according to the researchers.

"PKCe may be a new drug target for the development of a new class of (anti-anxiety) drugs that hopefully will not be sedating," Messing said.

But since the research was carried out in mice, there is still a lot of work to do, the California researcher pointed out. Messing said that he and his colleagues need to "do some studies in mice in which we can turn on and off PKCe in the brain to be certain the behavior is not a developmental quirk due to loss of PKCe throughout life."

The scientists also want to figure out exactly how PKCe regulates GABA-A receptors. Messing added that he hopes a drug company will be interested in making a drug that blocks PKCe and testing its anti-anxiety effects.

That the researchers have identified a potential new target for anti-anxiety drugs is the "exciting take-home message" of the study, according to Dr. Joshua A. Gordon, of Columbia University in New York. Although he points out in an accompanying editorial that more work is needed to confirm how blocking PKCe reduces anxiety, according to Gordon, "it is attractive to imagine" that inhibiting this enzyme could make our brains more sensitive to its own anti-anxiety substances.

SOURCE: The Journal of Clinical Investigation 2002;110:915-917, 1003-1010.

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"It was once written "To thine own self be true". But how do we know who we really are? Every man must confront the monster within himself, if he is ever to find peace without. .." Outer Limits(Monster)