VUF-K-8788, a periphery-selective histamine H-1 antagonist with anti-pruritic activities

The pharmacological properties of 7-{3-[4-(2-quinolinylmethyl)-1-piperaziny l]-propoxy)-2,3-dihydro-4H-1,4-benzothiazin-3-one (VUF-K-8788) were investi gated in vitro and in vivo. WF-K-8788 inhibited [H-3]-mepyramine from bindi ng to the cell membrane of lung parenchyma (K-i value: 5.0 nM) and the hist amine-induced contraction of isolated guinea pig ileum (pA(2): 9.71) withou t affecting ileal contractions induced by acetylcholine, serotonin, KCl and BaCl2. The increase of vascular permeabilities induced by histamine and pa ssive cutaneous anaphylaxis (PCA) in guinea pigs were inhibited by VUF-K-87 88 in a dose-dependent fashion (ED50: 0.24 and 0.26 mg/kg, p.o., respective ly). Moreover, the anti-histaminic effect of VUF-K-8788 was also observed i n rats. In experiments on the effects on the central nervous system, WFK-87 88 at 1 mg/kg, p.o. hardly antagonized the Ill receptor at all in the cereb ral cortex of guinea pigs. VUF-K-8788 inhibited the PCA-induced scratching behavior completely without affecting thiopental-induced sleep in mice. The se results suggested that WF-K-8788 would be useful in the treatment of all ergic disorders such as atopic dermatitis and eczema.