A new candidate drug for bipolar disorder is being designed by researchers in Chicago and New York. It works as well in mice as do the currently prescribed drugs. They hope that it will ultimately provide relief without the side-effects of present treatments.
Bipolar disorder, which afflicts about 1% of adults, is typically treated with drugs called mood stabilizers, especially lithium is used. Lithium is thought to act by blocking the function of an enzyme called glycogen synthase kinase-3beta (GSK-3beta) in the brain.
Kozikowski and colleagues did two things. First, they looked for a way to improve binding to the enzyme. They also altered the enzyme so that it could get from the blood into the brain, which involves passing through a water-resistant membrane.
They made a whole family of molecules, and tested how well each of these blocked the enzyme’s chemical behavior. They identified the best of them and looked at whether it would work in animals. In a mouse model of ‘mania’, hyperactive mice were calmed and moved around much less when given the new candidate drug. The new compound looks promising, but a lot of work remains to be done before it will be ready for human trials.
1. Kozikowski, A. P. et al. J. Am. Chem. Soc. 129 , 8328-8332 (2007).