Tachykinins
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The tachykinins represent one of the most thoroughly investigated family of neuropeptides, whose members and receptors have been characterized at the genetic and molecular level and whose pharmacology has now been advanced to the first clinical application. These exciting accomplishments and prospects are reviewed and discussed in this volume in an authoritative manner. Particular emphasis is laid on the development of selective non-peptide antagonists for all 3 tachykinin receptors and their potential as novel drugs in a variety of diseases. The approval of the first tachykinin receptor antagonist as an antiemetic drug is particularly highlighted, and the utility of tachykinin receptor antagonists in affective disorders, chronic obstructive airway disease and irritable bowel syndrome, to name a few indications, is extensively considered.
More than 70 years have elapsed since U. S. von Euler and I. H. Gaddum dis covered an unidentified depressor substance in the brain and gut. The effects of the powdery extracts were marked as 'P' on the kymograph tracings, and the nondescript name of 'substance P' still carries the breath of this adventurous period. In the 1960s, substance P returned in another disguise, staging as a hypothalamic peptide that causes copious salivary secretion (see chapter by F. Lembeck and I. Donnerer). This time, though, the mysterious substance was tracked down by S. E. Leeman and her collaborators as an undecapeptide, after it had eluded its identification for some 40 years. Substance P turned out to be the mammalian counterpart of a family of peptides which had been extracted from amphibian and nonvertebrate species and which had been given the name 'tachykinins' by V. Erspamer. Soon novel members of this peptide family were discovered, and in mammals substance P was joined by neurokinin A and neu rokinin B. The presence of tachykinins in frog skin as well as in venoms and toxins of microbes and arachnids raises the possibility that these peptides re present an old system of biological weapons that have been transformed to a particular messenger system in mammals.
