Two New Compounds to Treat Addiction Cigarettes and Alcohol

Researchers at the Ernest Gallo Clinic and Research Center at the University of California, San Francisco, and Pfizer Inc., has determined that two new compounds may be effective in treating alcohol and nicotine dependence at the same time.

In a paper published in the November 3 issue of Neuropsychopharmacology 2010, the researchers showed that alcohol consumption in rats was significantly lowered by two compounds that are targeted to neuronal nicotinic acetylcholine receptor (nAChR) subtype of {alpha} 3 {beta} 4 *.

nAChRs are proteins found in the brain and central nervous system that mediate the broader effects of substances such as nicotine. A recent study of human genetics have shown that the gene encoding alpha} {subtype {3} beta4 * very significant for susceptibility to alcohol and nicotine dependence.

"This problem has been translating important genetic findings in a more effective treatment for humans," says co-senior author, Selena E. Bartlett, PhD, director of Preclinical Development group at the Gallo Center. The lead author of the study is Susmita Chatterjee, PhD, from the Gallo Center.
Work has been done in collaboration with scientists led by senior co-author, Hans Rollema, PhD, in Neuroscience Research Unit at Pfizer Inc.

One new compound, CP-601 932, has been declared safe in humans in a clinical study, notes Bartlett. He recommends a clinical study to evaluate the efficacy of compounds and the potential benefits in treating both alcohol and nicotine dependence.

Another compound is PF-4575180. Both were developed by Pfizer.
"Alcoholism and nicotine are often treated as a separate disorder," says Bartlett, "despite the fact that 60 to 80 percent of heavy drinkers also smoked tobacco. Very few effective strategies for treating these disorders separately, let alone simultaneously. Our data show that by targeting specific nAChR subtypes, it is possible to treat alcohol and nicotine dependence with one drug. "

While the compound has a significant impact on alcohol consumption in mice, sucrose intake has no effect. "This indicates that unlike other drugs already approved for the misuse of alcohol, these compounds do not interfere with the brain's natural pengimbalan system in a more broad," said Bartlett.
Co-author of the study are Pia Steensland of the Karolinska Institutet, Sweden; Jeffrey A. Simms and Joan Holgate of the Gallo Center, and Jotham W. Coe, Raymond S. Hurst, Christopher L. Shaffer and John Lowe of Pfizer.

The research was supported by funding from the National Institutes of Health, U.S. Department of Defense, State of California, the Foundation Boncompagni-Ludovisi BLANCEFLOR, née Bildt, the Swedish-American Foundation, and Insamlingsstiftelsen Hjärnfonden / Swedish Brain Foundation.

UCSF - affiliated Ernest Gallo Clinic and Research Center is one of the world's leading academic centers to study the biological basis of substance and alcohol use disorders. Gallo Center found a potential target molecules for therapeutic drug development that extended through the study of proof-of-concept clinical and preclinical.

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.