Department of Pharmacology
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Paul R. Pentel, M.D., Ph.D.
Professor of Medicine & Pharmacology
Few medications are available for the treatment of addictions, and their efficacy is limited. Addiction is a challenging target for medication because the brain pathways affected by addictive drugs also mediate many basic and essential functions such as cognition, memory, emotion, and pleasure. Attempts to modify these pathways with medications in order to block addiction invariably interfere with these essential functions, and this serves to limit the usable dose of the medications. An alternative treatment strategy is to target the addictive drug itself rather than the brain pathways it affects.
The Pentel lab has been studying the feasibility of targeting addictive drugs directly through immunization. Nicotine is the primary addictive component of cigarette smoke. Vaccination of rats with a nicotine-protein conjugate vaccine elicits the production of nicotine-specific antibodies which bind nicotine in serum and extracellular fluid and reduce or slow nicotine distribution to brain. Because the antibodies bind only nicotine, vaccination is devoid of side effects. Vaccination attenuates many of the effects of both acute and chronic nicotine, including behaviors relevant to nicotine dependence. Current efforts are directed at improving vaccine immunogenicity through better understanding the biology of the B cells that generate antibody, or by combining vaccination with other types of medications that have complementary actions. Parallel work is underway with an opioid vaccine. A related area of interest is identifying other components of tobacco smoke that contribute to addiction and their mechanisms of action.