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FR 113680: a novel tripeptide substance P antagonist with NK 1 receptor selectivity
Author(s) -
Morimoto Hiroshi,
Murai Masako,
Maeda Yasue,
Hagiwara Daijiro,
Miyake Hiroshi,
Matsuo Masaaki,
Fujii Takashi
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14303.x
Subject(s) - neurokinin a , substance p , tachykinin receptor , neurokinin b , guinea pig , medicine , endocrinology , receptor , chemistry , contraction (grammar) , biology , neuropeptide , biochemistry
1 We have discovered a novel tripeptide substance P (SP) antagonist, FR 113680 [N α ‐[N α ‐(N α ‐acetyl‐ l ‐threonyl)‐N′‐formyl‐ d ‐tryptophyl]‐N‐methyl‐N‐phenylmethyl‐ l ‐phenylalaninamide]. In binding experiments, FR 113680 inhibited [ 3 H]‐SP binding to guinea‐pig lung membranes (NK 1 ) in a competitive manner but had not effect on [ 3 H]‐SP binding to rat cerebral cortical membranes (NK 1 ), [ 3 H]‐neurokinin A ([ 3 H]‐NKA) binding to rat duodenum smooth muscle membranes (NK 2 ) and [ 3 H]‐eledoisin (Ele) binding to rat cerebral cortical membranes (NK 3 ). 2 In bioassay experiments, FR 113680 dose‐dependently inhibited SP‐induced guinea‐pig ileum contraction (NK 1 ), but did not inhibit either NKA‐induced rat vas deferens contraction (NK 2 ) or neurokinin B (NKB)‐induced contraction of rat portal vein (NK 3 ). According to Schild plot analysis, the inhibitory effect of FR 113680 on SP‐induced guinea‐pig ileum contraction is competitive and the pA 2 value is 7.53. 3 The inactivity of FR 113680 on NK 1 receptors in rat compared to guinea‐pig may represent species‐specific forms of the NK 1 receptor. 4 These findings suggest that FR 113680 interacts selectively with the NK 1 neurokinin receptor.