This paper describes several tactical issues that would advance discovery science and the translation to development. There is a need to broaden target discovery with respect to the disease mechanisms of tobacco addiction. Secondly, discovery and target validation needs to be done in a more integrated fashion; there is a need to apply existing models in concerted fashion, recognizing that tobacco addiction is a complex, multifac-eted disease. Discovery research would benefit immediately from the increased availability of molecular tools, both molecular probes for various receptor systems and compounds that can be used in human experimental laboratory studies to validate observations from cell, tissue and animal experiments. Fourth, tobacco addiction/dependence would benefit from broad agreement on its definition, its core elements and treatment targets for the disease. Finally, research with human subjects could make a greater contribution to target validation and to development, and improved networking of clinical trials sites could provide an appealing platform to augment development. The paper argues that advances in pharmacotherapies will be helped by collaborative activities, translational activities built upon existing knowledge, and partnership between publicly funded discovery researchers and the pharmaceutical industry.
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