Editorial [ Neuropeptide Y Receptors as Targets in Drug Discovery Guest Editor: Ambikaipakan Balasubramaniam ]

My daughter was borne in 1980, surely a good omen! At about the same time, I joined the University of Cincinnati as a fellow, and was looking for a new project in the GI hormone field and, coincidentally Tatemoto, the Man with Gold Fingers, added neuropeptide Y (NPY) and peptide YY (PYY) to his long list of polypeptide hormone discoveries. Since then, I have been working on NPY family of hormones and NPY peptides which, in turn, have served me well to date. The latter may also be true for most of my colleagues all over the world, who are privileged to meet every couple of years at the International Meetings on NPY. To be honest, I do not know much of anything else beyond NPY, Cincinnati, and my family! NPY (isolated from brain), PYY (isolated from intestine) and pancreatic polypeptide (PP) (isolated from pancreas) constitute the NPY/PP family of homologous hormones. Since its isolation, NPY has been described in various ways, depending on the site and function investigated. Some of these characterizations reveal normally reserved scientists reaching for superlatives: “NPY is the most abundant peptide in the brain;” “NPY is the most potent vasoconstrictor peptide isolated to date,” “NPY is the most powerful orexigenic peptide isolated to date.” These remarkable properties of NPY, especially the latter, spurred vigorous investigation of the properties of the NPY family of hormones. The last two and a half decades have seen the cloning of four functional receptors, denoted Y1, Y2, Y4 and Y5, the development of several useful receptor-specific ligands and the establishment of knock-out models for NPY and its various receptors. These tools have played key roles in delineating the receptor subtypes mediating various actions of NPY and also have provided strong evidence for the involvement of the NPY family of hormones in the pathophysiology of various conditions including obesity, cardiovascular and cardiac diseases, intestinal dysfunction, epilepsy and mental disorders. Thus, NPY receptors became obvious targets for drug development in the treatment of a variety of diseases. Moreover, a few pharmaceutical companies have recently initiated preliminary clinical or Phase I trials to determine whether NPY peptides have potential as anti-obesity drugs. For these reasons, the time is now appropriate for a special volume of Current Topics in Medicinal Chemistry dedicated to the “Potential of NPY Receptors as Targets in Drug Discovery.” In compiling this Special Volume on NPY, I have gathered contributions from experts on receptor targets that have been implicated unequivocally in diseases. In addition, I have also included chapters on emerging drug targets. A total of ten articles, including chapters on the clinical potential of NPY and its receptors in mental disorders, obesity, epilepsy, GI disorders, cancer, cardiac and cardiovascular diseases, and inflammatory and immune diseases are included in this volume. One of these chapters also describes how central leptin gene therapy could be exploited to beneficially alter hypothalamic NPY function. After a brief introduction, each chapter, based on the existing evidence, discusses the rationale(s) for developing NPY-based drugs, the receptor subtypes involved and the type of ligands (agonist/antagonist) that need to be developed. Most chapters conclude with a prospective of using NPY-based drugs to treat the concerned disease. In summary, this state-of-the-art volume on NPY Receptors as Targets for Drug Discovery will not only stimulate further research on the Clinical Potential of NPY, but will also serve as a “One-Stop Guide” on NPY-based drugs for those entering this field. I am certain that, with the advancement in peptidic- and non-peptidic drug delivery techniques, NPY based drugs will eventually be developed to treat a variety of diseases. I wish to express my sincere appreciation to all the authors for their outstanding contributions, and particularly for meeting their deadlines. I also thank Allen Reitz, Editor-in Chief, for asking me to edit this Special Volume on NPY.