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Biography

Neil E. Paterson completed his medical degree at the University of Aberdeen, Scotland, and then took up a postdoctoral position at The Scripps Research Institute in La Jolla, California. Following his Ph.D. at the University of Dundee, Scotland, he spent time at the University of California, San Diego, and the University of California, Los Angeles. Currently, he is a team-leader at PsychoGenics, Inc., contributing to discovery programs and fee-for-service activities in the areas of cognition, schizophrenia and abuse liability. He has authored more than 30 papers in peer-reviewed journals and several book chapters.

Abstract

Effective treatment of substance use disorders remains a largely unmet medical need, with a scarcity of efficacious therapeutics. There are a variety of treatment approaches currently in research and/or development, but some of the most effective Food and Drug Administration-approved addiction medications are partial agonists (for example, varenicline for nicotine dependence). An interesting aspect of these medications is their properties in preclinical abuse liability assays. Typically, the identification of certain behavioral properties in abuse liability assays raise a red flag in the development of novel chemical entities – but for partial agonists, those same properties are essential. The crucial distinction between an abused substance and a partial agonist addiction therapeutic lies in the degree to which the partial agonist mimics the abused substance. A brief review of abuse liability assays, previously highlighted by the FDA, is provided. Data are presented illustrating the demonstrated effects of varenicline in abuse liability assays and models of nicotine dependence. Interestingly, the atypical antidepressant bupropion, a first-line smoking cessation therapeutic, shares at least some of varenicline’s behavioral effects in preclinical abuse liability assays. Based on the characterization of partial agonist therapeutics in abuse liability assays, an ideal profile is presented for future development efforts, and additional attractive characteristics of novel addiction therapeutics are suggested.