Unlikely candidate helps alcohol-dependent mice cut back on the sauce.
Say what you will about glutamate-gated chloride channels in the parasitic nematode Haemonchus contortus—but the one thing you probably wouldn’t say about the cellular channels in parasitic worms is that a drug capable of activating them may prove useful in the treatment of alcoholism and other addictions.
When scientists go looking for drugs to use against addiction, they do not typically begin with a class of drugs that includes a medication for use against head lice and ticks. But that is exactly where the trail led Daryl Davies, co-director of the Alcohol and Brain Research Laboratory at the University of Southern California. Davies and his group were interested in a set of molecules in the brain known as P2X receptors. A subtype of these receptors, involved in ion channel gating, cease to function in the presence of ethanol. The researchers found that if you keep flooding the receptor with alcohol, these ion gates shut down permanently—an example of how alcohol abuse can change the brain.
Another compound that works on the same ion gate is ivermectin, an anti-parasitic medicine used around the world in humans and animals. As it turns out, ivermectin blocks the effect that alcohol has on P2X receptor subtypes. In recent research, the USC team demonstrated that alcohol-dependent mice drank half as much when they were also given ivermectin. This “newly identified alcohol pocket” is a mystery at present. But ivermectin does appear to work primarily on glutamate systems. (See previous post). For now, the researchers can’t say for certain why ivermectin makes mice drink less, but suspect it has something to do with how the brain signals that it’s time to stop drinking. Davies has speculated that a drug like ivermectin could be of use in treatment programs other than “abstinence-based models.” As Suzanne Wu reports in USC Trojan magazine, the team is now at work on other drugs based on ivermectin’s molecular structure. “If there was already a drug that was 95 percent effective, I might not be studying ivermectin,” Davies told the magazine. “I might not even be in the alcohol field. The funding for alcoholism research hasn’t caught up with the magnitude of the consequences of not finding a cure.”
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