| Popis: |
This chapter describes studies that are conducted based on a proactive nonclinical testing strategy, designed to carry out studies early in drug discovery and development. The conduct of these studies is driven by the realization that early, rather than late, attrition conserves valuable resources. When the abuse potential of a compound is not a showstopper, nonclinical information is used to plan for human abuse liability assessment; however, when abuse potential is a showstopper, early information enables redirection of resources. Early risk identification is the key and it was considered critical to not wait until regulatory agencies request the information, but rather be proactive and start early and use a signal system based on the available FDA guidance document. Issue resolution from three nonclinical projects is described. First, mGluR5 antagonists in development for multiple indications are discussed and include the identification of unique psychoactive effects in animals. Second, peripherally acting μ-opioids for analgesia are discussed and include the assessment of the role of speed of infusion for “peripherally acting” drugs and the implications for abuse liability. Third, δ-opioids designed for use in pain, anxiety, and depression are discussed and include the investigation of potential psychoactive properties based on indication-specific reference compounds. |
