Antagonists for Substance P and Other Neurokinins
Because of the numerous roles of neurokinins in physiology and physiopathology, antagonists for these peptides represent a new type of promising pharmacological tool (Rosell and Folkers, 1982). During the last 5 years, a fairly large number of compounds have been developed by various investigators (see references in Table I), and some prototypes of the various categories (undeca-, octa-, hepta-, or hexapeptides) are presented in Table I. From these results, it is evident that (1) all antagonists contain at least two D-amino acids (generally D-Trp in the positions 7 and 9), which are needed to confer to the peptide its antagonistic properties, (2) the N-terminal residues (either the first or the second) are replaced with D isomers (D-Arg1, D-Pro2 in the undecapeptide, D-Pro4 in the octapeptides) or with L isomers (Arg or Pro in the hepta and hexapeptides) in order to protect the antagonist from degradation or improve its solubility, and (3) the C-terminal Met has generally been replaced with an aliphatic (Leu, Nle) or aromatic (Phe) residue to increase the affinity of undeca-, octa-, and heptapeptide antagonists.
KeywordsTachykinin Receptor Bombesin Receptor Neurokinin Antagonist Mammalian Tachykinin Canadian Heart Foundation
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