Beta-Carbolines Could Reduce Alcoholics’ Impulse to Drink

A new animal study is offering hope that a class of compounds called beta-carbolines could treat alcoholism without many of the unwanted side effects caused by current therapies.

Beta-carboline compounds offer great promise for the treatment of alcoholism. Image credit: Imagens Evangelicas / CC BY 2.0.

“Alcoholism is a major problem in the United States. Alcohol abuse costs almost $220 billion to the U.S. economy every year. That’s a shocking number. We need a better treatment right now,” said study lead author Phani Babu Tiruveedhula from the University of Wisconsin, Milwaukee.

The exact causes of alcoholism are not well understood, but scientists explain that the urge to drink is related to the brain’s pleasure centers. They have found that alcohol triggers the brain to release dopamine, the same neurochemical whose levels increase in response to pleasurable behavior.

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 co-author Dr James Cook, also from the University of Wisconsin, Milwaukee.

“But these medications, derived from a class of compounds called opioid antagonists, cause depression in some patients. And they’re 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, Tiruveedhula and co-authors focused on beta-carboline compounds known to cause some of the same results as Valium and the opioid antagonists without the unwanted side effects.

In tests using rats bred to crave alcohol, they found that administering these compounds drastically diminished the rats’ drinking.

What’s more, 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 animals.

Because this is different from what is seen with current drugs, the scientists 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,” Dr Cook said.

“If everything works out, a drug could be ready for the market in 5 – 6 years,” he added.

The scientists reported their results August 19 at the 250th National Meeting & Exposition of the American Chemical Society in Boston, MA.

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V. Tiruveedhula et al. 2015. Design and regiospecific synthesis of 3-substituted beta-carbolines as a GABAA subtype selective agents for the treatment of alcohol abuse. 250th National Meeting & Exposition of the American Chemical Society, article # 433