ABSTRACT
This chapter discusses the medicinal chemistry which enabled discoveries in each of these three areas. In addition, it examines newly emerging antagonists at several other peptide receptors. Nonpeptide antagonists have also been useful in defining the physiological role of neurokinin A binding to the NK2 receptor and the potential for therapeutic intervention at this target. The nonpeptide antagonists for the cholecystokinin, angiotensin II, and tachykinin receptors reviewed have enabled delineation of receptor subtypes and evaluation of the relevant physiological roles of these peptides. With rapid advances enabling cloning of G protein-coupled receptors for peptides and the discovery of nonpeptide antagonists for these receptors, the stage is set for a powerful combination of molecular genetics with medicinal chemistry to elucidate the mechanism of receptor antagonist action. Finally, the chapter considers contributions from the field of molecular biology which have characterized details of the binding of antagonists at peptide receptors and may some day enable design of new antagonists.
