Gallo research shows new compounds may treat both
alcohol and cigarette addictions 
Source: UCSF press release
Date: November 3, 2010
Researchers at the Ernest Gallo Clinic and Research
Center at the University of California, San Francisco,
and Pfizer Inc., have determined that two new compounds
may be effective in treating both alcohol and nicotine
dependence at the same time.
In a paper published in the November 3, 2010 issue
of Neuropsychopharmacology, the researchers
showed that alcohol consumption in rodents was
significantly decreased by two compounds that target
neuronal nicotinic acetylcholine receptor (nAChR)
subtype α3ß4*.
nAChRs are proteins found in the brain and broader
central nervous system that mediate the effects of
substances such as nicotine. Recent human genetic
studies have shown that the genes encoding the α3ß4*
subtype are of significant importance for
susceptibility to both alcohol and nicotine
dependence.
“The problem has been translating these important
genetic findings into more effective medications for
people,” said co-senior author Selena E. Bartlett,
PhD, director of the Preclinical Development group at
the Gallo Center. The lead author of the study is
Susmita Chatterjee, PhD, of the Gallo Center.
The work was done in collaboration with scientists
led by co-senior author Hans Rollema, PhD, in the
Neuroscience Research Unit at Pfizer Inc.
One of the new compounds, CP-601932, has been shown
in a clinical study to be safe in humans, notes
Bartlett. She recommends a clinical study to evaluate
the compound’s efficacy and potential benefits in
treating both alcohol and nicotine dependence.
The other compound is PF-4575180. Both were
developed by Pfizer.
“Alcohol and nicotine addiction are often treated
as separate disorders,” Bartlett says, “despite the
fact that 60 to 80 percent of heavy drinkers smoke
tobacco. There are very few effective strategies for
treating these disorders separately, let alone
together. Our data suggest that by targeting specific
nAChR subtypes, it may be possible to treat both
alcohol and nicotine dependence with one
medication.”
Significantly, while the compounds had a significant
effect on the rodents’ alcohol consumption, their
intake of sucrose was not affected. “This indicates
that unlike currently approved alcohol abuse
medications, the compounds do not interfere with the
brain’s natural reward system in a larger way,”
says Bartlett.
Co-authors of the study are Pia Steensland, PhD, of
the Karolinska Institutet, Sweden, Jeffrey A. Simms,
BSc, and Joan Holgate, BSc, of the Gallo Center, and
Jotham W. Coe, PhD, Raymond S. Hurst, PhD, Christopher
L. Shaffer, PhD, and John Lowe, PhD, of Pfizer.
The study was supported by funds from the National
Institutes of Health, the US Department of Defense, the
State of California, the Foundation BLANCEFLOR
Boncompagni-Ludovisi, née Bildt, the Sweden-America
Foundation, and Insamlingsstiftelsen Hjärnfonden/The
Swedish Brain Foundation.
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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