FDA-Approved Drug Shows Promise as Alcoholism
Treatment
Source: UCSF press release
Date: January 11, 2011
A medication commonly prescribed as a muscle
relaxant shows promise as a potential treatment for
alcoholism, based on a study in rats by researchers at
the Ernest Gallo Clinic and Research Center and the
University of California, San Francisco.
Chlorzoxazone, an FDA-approved drug, significantly
decreased alcohol consumption in a rat model of heavy
drinking, said lead author Woody Hopf, PhD, an
associate investigator at Gallo and an assistant
adjunct professor of neurology at UCSF.
The study appeared online in Biological Psychiatry
(Jan. 3, 2011).
Hopf and his colleagues found that, among rats that
have been trained to drink large amounts of alcohol,
chlorzoxazone activates the SK-type potassium channel
in neurons, which makes the neurons less excitable. The
drug’s action takes place in the nucleus accumbens, a
brain region that in both rodents and humans is part of
the reward system that affects craving for alcohol and
other addictive substances.
The ability of chlorzoxazone to reduce neuronal
excitability is “important,” Hopf explained,
“because the more excitable neurons in the nucleus
accumbens are, the more they respond to the stimulation
provided by alcohol, which in turn drives
alcohol-seeking behavior.”
Applying the results of his previous research to the
current study, Hopf found that rats that habitually
drink heavily have fewer SK channels in their neurons
than rats without an alcohol habit. In the current
study, Hopf demonstrated that when the rats’
remaining SK channels were activated, “the
excitability of the nucleus accumbens was turned down,
and this, in turn, suppressed alcohol drinking in
heavy-drinking rats.”
Hopf sees chlorzoxazone as a possible alcohol-abuse
medication among patients for whom currently available
drugs do not work, or among patients who do not take
the drugs because of adverse or unpleasant side
effects. In particular, “this might work for an
alcoholic who is in abstinence, and who is doing OK,
but who during a critical or stressful period is in
danger of going back to drinking,” said Hopf.
“Chlorzoxazone might be exactly the kind of drug to
take the edge off that craving, without side
effects.”
Hopf said that the next logical step in his research
is a clinical trial, “which could begin
immediately,” since chlorzoxazone is already approved
as a medication. He says the trial could be conducted
by the Gallo Center, “since we have an in-house
clinical trials group with tremendous expertise.”
Co-authors of the study are Jeffrey A. Simms, BS,
Shao-Ju Chang, BA, Taban Seif, PhD, and Selena E.
Bartlett, PhD, of the Gallo Center, and senior author
Antonello Bonci, MD, an adjunct professor of neurology
at the Gallo Center and UCSF and Scientific Director of
the Intramural Research Program at the National
Institute on Drug Abuse.
The study was supported by funds from the National
Institute on Alcohol Abuse and Alcoholism, the State of
California, and the U.S. Department of Defense.
The UCSF-affiliated Ernest Gallo Clinic and Research
Center is one of the world’s preeminent academic
centers for the study of the biological basis of
alcohol and substance use disorders. Gallo Center
discoveries of potential molecular targets for the
development of therapeutic medications are extended
through preclinical and proof-of-concept clinical
studies.
UCSF is a leading university dedicated to promoting
health worldwide through advanced biomedical research,
graduate-level education in the life sciences and
health professions, and excellence in patient care.
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