Posted by utopizen on December 14, 2002, at 0:27:07
Tamoxifen
Tamoxifen (Nolvadex), the non-steroidal anti-estrogen drug used to treat or prevent breast cancer, may be effective in treating acute mania in patients with bipolar disorder. Although the report is small and preliminary, results are encouraging, and further studies are planned.
In a single-blind case series, Husseini K. Manji, M.D., recipient of a NARSAD 1998 Independent Investigator Award and the 1999 Falcone Prize for Affective Disorders Research, and colleagues report on seven patients with bipolar I disorder and acute mania who received tamoxifen in doses ranging from 20 to 80 mg daily for three weeks.
Like lithium and valproate, tamoxifen affects protein kinase C (PKC). PKC plays a pivotal role in regulating neuronal excitability, neurotransmitter release and long-term synaptic events, according to Manji. Tamoxifen is the only selective PKC inhibitor available for human use.
The study sought to determine if tamoxifen would have a faster on-set of action than lithium or valproate, which can take days or even weeks to work.
While lithium and valproate are not chemically similar, they have similar effects on PKC, which led Manji and his colleagues to question if dampening PKC faster would result in treating mania faster.
The recommended daily dose in product labeling for breast cancer is 20 to 40 mg daily. Manji reports that most patients needed 60 to 80 mg per day by mouth to inhibit PKC.
The results show significant changes in scores of the Young Mania Rating scale (YMRS), and Clinician Administered Rating Scale for Mania (CARS-M). Researchers stress tamoxifen is not a long-term treatment, but rather for fast stabilization of acutely manic patients.
Only one patient reported an adverse effect, mild flushing on dose titration. The patient was able to tolerate a dose of 60 mg daily.
Manji says a larger, double-blind study of tamoxifen vs. lithium or valproate is planned to begin during the summer of 2000. Data should be available within two years.
Adapted with permission from Manisses Communications Group 800-333-7771
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Study Finds New Seat of Anxiety in BrainDiscovery may lead to development of better drugs
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•Family & friendsTHURSDAY, 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 disord
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so, um, inhibitors, they would regulate, or increase, Kinase? Increase = anxiety, right??
poster:utopizen
thread:131753
URL: http://www.dr-bob.org/babble/20021210/msgs/131753.html