Investigation of the specificity of FK 888 as a tachykinin NK1 receptor antagonist

Abstract

A recently described peptide tachykinin (NK1) receptor antagonist, FK 888, was found to inhibit the electrically‐evoked, tachykinin‐mediated contractile responses of the rabbit iris sphincter in a concentration‐dependent manner; the pIC50 value was 6.6 ±0.08. Contractions induced by a selective NK1 receptor agonist, [Sar9, Met(O2)11]substance P, were inhibited competitively by FK 888; the pKB value was 7.1. FK 888 (1 nm‐100 μm) was without effect on the electrically‐evoked, cholinergic response of the rabbit iris sphincter and the electrically‐evoked, sympathetic response of the guinea‐pig vas deferens. The contractions of the rabbit iris sphincter, induced by either carbachol (10 nm‐30 μm) or noradrenaline (0.1–100 μm), were not affected by 10 μm FK 888. FK 888 (1–30 μm) did not induce histamine release from rat peritoneal mast cells. FK 888 (33 and 333 μm) was without effect on the electrically‐evoked action potentials of the frog sciatic nerve. Thus, FK 888 is a moderately high affinity and selective tachykinin (NK1) receptor antagonist. 1994 British Pharmacological Society