Preface [Hot Topic: Recent Advances in Neurokinin Receptor Antagonists (Guest Editor: Ashok B. Shenvi)].

The observation by Von Euler and Gaddum in 1931 that an extract of horse intestine and brain causes peripheral vasodilatation and contraction of intestinal muscles set stage for a number of studies which ultimately lead to the determination of the amino acid sequence of the first member of mammalian tachykinins namely substance P in 1971. Since then two additional tachykinins from mammalian source, neurokinin A and neurokinin B, have been identified. All these peptides share the Cterminal pentapeptide FXGLMa and their family name tachykinin refers to the ability to induce fast, immediate contractile responses of smooth muscle preparations. The receptors that substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) bind are referred to as NK1, NK2 and NK3 receptors respectively.Mammalian tachykinins are derived from two precursor-encoding genes. As a consequence of alternative processing of RNA and polypeptide precursors, there exists a tissue-specific difference in the expression of these peptides. Tachykinins are multifunctional peptides and modulate a variety of biological activities through G-protein coupled receptors. In the central nervous system, they contribute to central cardiovascular regulation, to the control of motor activity and the rate of respiration. Their presence in the hypothalamus and in the pituitary gland suggests a role in the control of neurosecretion. These peptides also exhibit a variety of peripheral activities. They are involved in nociceptive and pain transmission and perception. They cause vasodilatation, salivation and both exocrine and endocrine pancreatic secretion. They are implicated in regulation of nerogenic inflammation, gastrointestinal motility and pulmonary function. They are present in immune cells.Because of the involvement of tachykinins in several pathophysiological events considerable effort is invested in the discovery of antagonists that will be useful drugs in the treatment of human diseases. We have attempted to review some of the latest developments in this area. The following three reviews deal with the NK1, NK2 and non-selective NK antagonists. Background information is included when needed to keep the discussion in proper perspective. It is our hope that these timely reviews will be useful to practicing medicinal chemists interested in the modulation of tachykinin activity to meet unmet medical needs.