An oral drug that treats alcoholism and has very few side-effects may be available in five to six years, according to scientists, including one of Indian-origin, who have identified compounds that drastically reduced drinking in rats.
The exact causes of alcoholism are not well understood, but the urge to drink is related to the brain's pleasure centres, according to V V N Phani Babu Tiruveedhula, a graduate student at the University of Wisconsin, Milwaukee.
Alcohol triggers the brain to release neurochemical dopamine. Some drugs currently available to treat alcoholism are aimed at dopamine.
"They dampen out the dopamine system a little bit, so you don't get so happy when you have an alcoholic beverage," said James Cook, a chemist at the University of Wisconsin, who advises Tiruveedhula.
However, these medications, derived from a class of compounds called opioid antagonists, cause depression in some patients, Cook said.
They are addictive themselves, which can lead to drug abuse. Valium is an example of another common drug used to treat alcoholism that is also addictive.
Looking for an alternative, Cook focused on molecules known to cause some of the same results as Valium and the opioid antagonists without the unwanted side effects.
For almost two decades, Cook collaborated with the late Harry June, a psychopharmacologist at Howard University. They conducted laboratory tests to understand the effects of these new compounds and to discover which ones work best.
Tiruveedhula has now made several promising beta-carboline compounds that could represent the future of alcoholism treatment. He simplified their manufacture from eight steps to just two, while increasing the yield tenfold and eliminating unwanted byproducts.
Cook said these potential medications could be taken orally.
In tests using rats bred to crave alcohol, the scientists found that administering these compounds drastically diminished the rats' drinking.
They observed very few of the side effects common to alcoholism treatment drugs, such as depression and losing the ability to experience pleasure. The drugs appeared to reduce anxiety in "alcoholic" rats, but not in control rats.
This is different from what is seen with current drugs, so researchers think the result hints that the new compounds work much differently than opioid antagonists. As such, the beta-carbolines may also be less addictive.
"What excites me is the compounds are orally active, and they don't cause depression like some drugs do," said Cook.
The group is testing the compounds in additional animal studies. Cook has patented several of the most promising compounds, and he is starting to explore possible partnerships with drug makers that could lead to medications.
If everything works out, Cook said, a drug could be ready for the market in five to six years.
