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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 3 of 3. This is the beginning of the thread.
Posted by utopizen on October 14, 2002, at 19:47:00
Just when I'm about to go mad on how sedating .5mg of Klonopin is for me...
-----------------------------------------------Study Finds New Seat of Anxiety in Brain
Discovery may lead to development of better drugs
THURSDAY, Oct. 10 (HealthScoutNews) -- American researchers have identified a new target area in the brain for anti-anxiety drugs.They report their findings in the October issue of The Journal of Clinical Investigation.
The discovery may lead to new kinds of non-addictive anti-anxiety drugs with fewer side effects.
Mice missing an enzyme called protein kinase Ce (PKCe) had significantly lower anxiety and stress compared to normal mice, the study says.
The researchers believe this finding can be applied to humans and help in creating better drugs to treat anxiety disorders.
"To conduct this study, we used a strain of mouse that lacks an enzyme called protein kinase Ce (PKCe). Earlier work showed that this enzyme interacts with GABA A receptors in the brain. As activation of GABA A receptors reduces anxiety, we tested whether PKCe deficiency reduces anxiety. This research demonstrated that a complete absence of the enzyme greatly reduces anxiety," says study co-author Jacob Raber, an assistant professor of behavioral neuroscience at the Oregon Health and Science University School of Medicine.
"While there are anxiety medications such as Valium currently on the market, these pharmaceuticals often act as a sedative. Even more concerning, many anxiety medications are addictive in nature. We believe this enzyme may be an ideal drug target for medications without serious side effects," Raber says.
He and his colleagues compared the responses of mice bred to lack PKCe and normal mice to various settings and conditions. Mice lacking PKCe were less timid about being in open, lighted areas and showed less stress when place in a confined space for a limited period.
An estimated 30 million Americans suffer from anxiety severe enough to require treatment. Anxiety disorders are the most common mental illness in the United States. People with anxiety disorders are three to five times more likely to see their doctor and six times more likely to be hospitalized for psychiatric disorders than other people.
Posted by temoigneur on October 15, 2002, at 14:49:34
In reply to News: Study Finds New Seat of Anxiety in Brain, posted by utopizen on October 14, 2002, at 19:47:00
Keen eye utopizen I'm posting an article that with the same info yours did, plus it has contact numbers - perhaps if some of us could reach the researchers and find out if there was any substance on the market right now that could inhibit PKCe, we could take the leap in treatment sooner than later. To say it's a long shot is the understatement of the decade, but "a journey of 1000 miles......."
University of North Carolina at Chapel Hill
2-Oct-02
Promising New Target for Anxiety-Reducing Drugs
Library: MED
Keywords: ANXIETY-REDUCING DRUGS ENZYME PROTEIN KINASE
Description: But when anxiety grows excessive -- as it does in an estimated 25 percent of U.S. residents sooner or later -- it can significantly reduce one's quality of life, and in the cases of some 20 million Americans at any given time, it reaches levels that may require treatment. (J. of Clinical Investigation, Oct-2002)
NEWS
Embargoed until 12:01 a.m. Oct. 1, 2002 -- No. 529
Wednesday, Oct. 2Researchers find promising new target for anxiety-reducing drugs
By DAVID WILLIAMSON
UNC News Services(Embargoed) CHAPEL HILL -- Anxiety, a natural response to real or potential threats, affects all higher creatures, including humans, sometime in their lives. Under normal conditions, that protective emotion spurs action to avoid such threats.
But when anxiety grows excessive -- as it does in an estimated 25 percent of U.S. residents sooner or later -- it can significantly reduce one's quality of life, and in the cases of some 20 million Americans at any given time, it reaches levels that may require treatment.
"We have effective compounds already for treating anxiety that are some of the most commonly prescribed medications worldwide," said Dr. Clyde W. Hodge, associate professor of psychiatry at the University of North Carolina at Chapel Hill School of Medicine. "Among these are benzodiazepines, such as Valium. The problem with them, however, is that they act as sedatives, which often prevent people from functioning normally. And people can become addicted to them."
As a result, he said, a worldwide search is on for less disruptive alternatives.
Working with colleagues at the University of California at San Francisco, Hodge now may have good news about that search.
"What we've done is to identify a potential new target in the brain for new, less problematic anxiety-reducing medications of the future," Hodge said.
Combining genetic, drug and behavioral studies in mice, he and his colleagues have found that mice lacking a form of the enzyme protein kinase C (PKC-epsilon) are extremely sensitive to their brains' own calming neurosteroid compounds and show significantly less anxiety than normal mice with PKC-epsilon, he said. The scientists conclude that inhibitors of PKC therefore may be useful in treating anxiety.
A report on the findings appears in the October issue of the Journal of Clinical Investigation. Besides Hodge, who is lead author, contributors include Drs. Jacob Raber now of Oregon Health and Science University in Portland, Robert O. Messing of the Ernest Gallo Clinic and Research Center at the University of California at San Francisco, who generated the genetically altered mice, and A. Leslie Morrow of UNC. Hodge and Morrow are members of UNC's Bowles Center for Alcohol Studies.
"In a paper in Nature Neuroscience in 1999, we showed that 'knockout' mice -- laboratory animals raised after their gene for PKC-epsilon had been intentionally disabled -- were super sensitive to modulation, or manipulation, of GABA, the number one inhibitory neurotransmitter in both mice and humans," he said. "As a result, they were more sensitive to alcohol and other drugs like Valium that alter GABA function. That led us to speculate about anxiety."
In new experiments involving mazes that both normal mice and mice with 'knocked out' PKC-epsilon scurried around in, researchers found the latter to be considerably less timid about open lighted areas and heights. The specially created rodents acted as if they already had been given medications to reduce their natural timidity, and they demonstrated a blunted response to stress as shown by lower stress hormone levels.
"The knockout mice also were more sensitive to a naturally occurring compound, allopregnanolone, which is called a neuroactive steroid and which alters GABA receptor function and hence has a calming effect," Hodge said. "GABA is what most of the known anxiety-lessening drugs act on in humans."
While obviously it would not be possible or desirable to knock out the PKC gene in humans, he said, medications could be developed that selectively inhibit PKC epsilon and modulate GABA differently from the existing imperfect drugs such as benzodiazepines with their sedative and addictive side effects.
"We don't know that yet, but this work gives us new hope," the scientist said.
In an accompanying commentary, Dr. Joshua A. Gordon of the Center for Neurobiology and Behavior at Columbia University's psychiatry department, praised the new findings.
"The exciting take-home message ... is the idea that PKC should be considered as a potential target for (anxiety-reducing) therapy," Gordon wrote. "...It is attractive to imagine that PKC blockade would result in (anxiety reduction) by making our brains more sensitive to our own (naturally occurring compounds for keeping anxiety under control)."
The new research was supported by the State of California and various National Institutes of Health, including the National Institute for Alcoholism and Alcohol Abuse, grants to Hodge, Messing and Raber.
- 30 -
Note: Hodge can be reached at (919) 843-4823, Messing at (510) 985-3950 and Gordon at (212) 543-5309.
Contact: David Williamson, (919) 962-8596
, there Utopizen, Below I'm
Posted by Shawn. T. on October 15, 2002, at 16:03:08
In reply to potential Breakthrough in anxiety trtmt, contacts, posted by temoigneur on October 15, 2002, at 14:49:34
A selective PKC epsilon inhibitor does not yet exist. You should realize that no one knows how a drug like that would affect humans, especially with long-term use. If it does turn out to work well, it will still be many years before you see a PKC epsilon inhibitor on the market. Drugs that are closer on the horizon are cholecystokinin B (CCK2) receptor antagonists for panic attacks and anxiety. Some of these drugs are in clinical trials and are based on genetic data rather than knockout mice with a supersensitivity to alcohol. I know that Glaxo is developing some drugs like this, and I'm sure that other drug companies probably are as well. The link is to a comprehensive review of CCK.
Shawn
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