Yanagihara Y, Abe T, Edanami K, Agata M, Kuroda T, Shida T
Clinical Research Center for Allergy, National Sagamihara Hospital, Kanagawa, Japan.
Arzneimittelforschung. 1988 Jan;38(1):70-4.
The effects of butyl 3'-(1H-tetrazol-5-yl)oxanilate (WP-833), a new antiallergic drug, on type I to type IV allergic reactions were investigated by employing various animal models. WP-833 (i.v. and p.o.) dose-dependently inhibited homologous or heterologous passive cutaneous anaphylaxis (PCA) mediated by rat or mouse immunoglobulin E (IgE) in rats. Homologous PCA caused by guinea pig IgE was also inhibited by WP-833. In addition, WP-833 had inhibitory actions upon homologous PCA induced by rat or guinea pig IgG. However, WP-833 showed no inhibition of rat skin reactions caused by histamine, serotonin and bradykinin, contrasting with the inhibition of prostaglandin E1-induced skin reaction. Furthermore, both adrenalectomy and propranolol treatment exerted no influences on the inhibition of IgE-mediated homologous PCA in rats by WP-833. In contrast to above findings demonstrating that WP-833 clearly inhibited type I allergic reaction, systemic Forssman shock in guinea pigs and reversed cutaneous anaphylaxis in rats (type II), passive Arthus reaction in rats (type III), and contact dermatitis and tuberculin reaction in mice (type IV) were unaffected by WP-833 even in higher doses than in those capable of completely inhibiting type I allergic reaction.
采用多种动物模型研究了新型抗过敏药物3'-(1H-四氮唑-5-基)氧杂环戊酸丁酯(WP-833)对I型至IV型过敏反应的影响。WP-833(静脉注射和口服)剂量依赖性地抑制大鼠体内由大鼠或小鼠免疫球蛋白E(IgE)介导的同种或异种被动皮肤过敏反应(PCA)。WP-833也抑制豚鼠IgE引起的同种PCA。此外,WP-833对大鼠或豚鼠IgG诱导的同种PCA有抑制作用。然而,与对前列腺素E1诱导的皮肤反应的抑制作用相反,WP-833对组胺、5-羟色胺和缓激肽引起的大鼠皮肤反应没有抑制作用。此外,肾上腺切除术和普萘洛尔治疗对WP-833抑制大鼠IgE介导的同种PCA均无影响。与上述表明WP-833能明显抑制I型过敏反应的结果相反,即使在高于完全抑制I型过敏反应剂量的情况下,WP-833对豚鼠全身性福斯曼休克、大鼠皮肤过敏反应逆转(II型)、大鼠被动阿图斯反应(III型)以及小鼠接触性皮炎和结核菌素反应(IV型)均无影响。