Safety Pharmacology in Drug Discovery and Development.

Safety pharmacology is essential throughout the spectrum of drug discovery and development. Prior to first-in-human studies, safety pharmacology assays, tests, and models predict the clinical risk profile of a potential new drug. During clinical development, safety pharmacology can be used to explore--and potentially explain--both predicted and unpredicted side effects (e.g., adverse events, changes in vital signs, abnormal laboratory values) in order to refine the original clinical risk profile. This chapter will introduce the reader to safety pharmacology's role in translational medicine: the science of translating potential drugs' on- and off-target nonclinical properties to clinical consequences in order to select the best drug candidates to move into early clinical testing. Case studies will be used to illustrate the importance of safety pharmacology testing throughout all phases of drug development.

Migraine therapy:seamlessness between plant-derived and synthetic drugs.

Migraine has been endemic for many centuries. Seamlessness between plant-derived and synthetic migraine therapies is evident in three major aspects: (A) The latter are molecular adaptations of the former, (B) Combinations of herbal and non-herbal migraine therapies (e.g., one for prophylaxis and the other for acute therapy) are used by many patients, and (C) All migraine treatments, whether plant-derived or not, are capable of clinical trial using the same endpoints. At least two, newly discovered plant-derived migraine therapies are currently under research using standard clinical trial methodology. Suggestions are provided for more flexible clinical trial designs that might particularly suit research into herbal remedies. The future of migraine therapy is likely to continue to exhibit an intimate, symbiotic relationship between plant-derived and synthetic drugs.