Effect of a new dual neurokinin antagonist on airway smooth muscle in situ.
The effect of FK224 (N-(N2-[N-¿N-(N-2,3-didehydro-N-methyl-N-[N-3- (2-pentylphenyl)-propionyl¿-L-threonyl]tyrosyl-L-leucynyl)-D -phenylalanyl¿-L-allothreonyl]-L-asparaginyl)-L-serine-v-lacto ne, CAS 125787-94-2) on isometric contraction of canine tracheal smooth muscle in situ was studied. Contraction was induced by administration of substance P, neurokinin A, and neurokinin B intra-arterially into the tracheal circulation in five mongrel dogs. FK224 inhibited substance P- and neurokinin A-induced contraction in a dose-dependent manner, but it did not inhibit neurokinin B-induced contraction significantly. These data suggest that FK224 is a dual antagonist of both neurokinin 1 and neurokinin 2 receptors, with a similar potency in in vivo experiments.
Shioya
T
T
Second Department of Internal Medicine, Akita University School of Medicine, Japan.
Kagaya
M
M
Sano
M
M
Itaba
M
M
Shindo
T
T
Fujii
T
T
Miura
M
M
D000818:Animals; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D015288:Neurokinin A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015287:Neurokinin B / Q000037:antagonists & inhibitors / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010456:Peptides, Cyclic / Q000494:pharmacology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D012137:Respiratory System / Q000187:drug effects*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D064729:Neurokinin-1 Receptor Antagonists; D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2; C075570:FK 224; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B