Conventional Behavioral Models and Readouts in Drug Discovery: The Importance of Improving Translation

This chapter describes the relevance and importance of preclinical models and readouts in the drug development process. Recently, animal behavioral models have been criticized on their role in the poor translation into novel pharmacotherapies. The first section addresses the importance of validity, ethics, and model/readout selection in preclinical behavioral pharmacology. As an example, models and readouts in the preclinical development of analgesic drugs for inflammatory and neuropathic pain are described. Furthermore, evoked and nonevoked pain readouts are reviewed. In the second section, the shortcomings of conventional preclinical models are discussed, and the necessity of improving translation in CNS drug discovery and development are also discussed. Several steps are proposed that could enhance translation from animal data to clinical efficacy. In this regard, neuroimaging and PK-PD modeling strategies are posed as crucial aspects in generating more valid, robust, reliable preclinical data resulting in more effective and translatable therapies. In conclusion, applying classical pharmacology to problems of translational medicine will aid us in improving the way we think about and use animal models. Closer collaboration and cross-over between clinical, pathological, and pharmacological research are paramount in optimizing the success of preclinical translation into novel medicines for patients in need worldwide.