Abstract:  The seminar will describe a short background on the undecapeptide neurotransmitter Substance P and the work done at Merck Research Laboratories to discover small molecule, non-peptidic, orally active, brain pentrant antagonists as potential drug entities to control pain, depression, asthma, arthritis, migraine and emesis. The in vitro and in vivo pharmacology as well as the medicinal chemistry and the clinical trials that led to the selection of Emend as a launched drug will be described. This case history will put into perspective the complex multi-disciplinary hurdles that need to be overcome to identify medicinal targets, identify lead molecules, convert them into molecules with drug-like properties, and to develop them as a launched drug.