Leibowitz M, Gordon R J, Wolf P S, Sonnino-Goldman P
Arch Int Pharmacodyn Ther. 1984 Sep;271(1):135-54.
REV 3164 has been evaluated in a variety of intact rodent models to reveal potential utility in the prophylactic treatment of asthma. REV 3164 was found a potent, orally active inhibitor of rat (IgE) passive cutaneous anaphylaxis (PCA, ED50 = 0.9 mg/kg). By contrast, at 50-200 mg/kg p.o., it did not affect guinea-pig (IgG1) PCA. In PCA rats, both REV 3164, 1-36 mg/kg i.p., and the known inhibitor of mast cell mediator release, disodium cromoglycate (DSCG), 2-54 mg/kg i.p., blocked cutaneous wheals caused by i.v. antigen challenge but not by intradermal serotonin or histamine. Neither REV 3164 (0.1-10 mg/kg i.p.) nor DSCG (2-54 mg/kg i.p.) affected Compound 48/80-induced wheals. REV 3164 (0.01-1 mg/kg i.v. or 10 mg/kg i.p.) abolished rat (IgE) passive lung anaphylaxis (PLA, ED50 = 0.05 mg/kg i.v. for inhibition of elevated airway resistance). At 10 mg/kg i.p., REV 3164 did not affect active lung anaphylaxis in guinea-pigs pharmacologically manipulated to enhance the production and action of slow reacting substance of anaphylaxis (SRS-A), nor did it exhibit anticholinergic activity in the rat. REV 3164 (100 mg/kg i.p.) did not protect conscious guinea-pigs from histamine aerosol-induced collapse. It is concluded that REV 3164 is an oral inhibitor of IgE-dependent immediate hypersensitivity in the rat with biological activities in rats and guinea-pigs similar to DSCG.
已在多种完整的啮齿动物模型中对REV 3164进行了评估，以揭示其在哮喘预防性治疗中的潜在效用。发现REV 3164是大鼠（IgE）被动皮肤过敏反应（PCA，半数有效剂量[ED50]=0.9毫克/千克）的一种强效口服活性抑制剂。相比之下，口服剂量为50-200毫克/千克时，它不影响豚鼠（IgG1）PCA。在PCA大鼠中，腹腔注射剂量为1-36毫克/千克的REV 3164和腹腔注射剂量为2-54毫克/千克的已知肥大细胞介质释放抑制剂色甘酸钠（DSCG），均可阻断静脉注射抗原激发引起的皮肤风团，但不能阻断皮内注射5-羟色胺或组胺引起的皮肤风团。REV 3164（腹腔注射剂量为0.1-10毫克/千克）和DSCG（腹腔注射剂量为2-54毫克/千克）均不影响化合物48/80诱导的风团。REV 3164（静脉注射剂量为0.01-1毫克/千克或腹腔注射剂量为10毫克/千克）可消除大鼠（IgE）被动肺过敏反应（PLA，静脉注射抑制气道阻力升高的半数有效剂量为0.05毫克/千克）。腹腔注射剂量为10毫克/千克时，REV 3164对经药理学处理以增强过敏反应慢反应物质（SRS-A）产生和作用的豚鼠主动肺过敏反应没有影响，在大鼠中也未表现出抗胆碱能活性。腹腔注射剂量为100毫克/千克的REV 3164不能保护清醒的豚鼠免受组胺气雾剂诱导的虚脱。得出的结论是，REV 3164是大鼠中IgE依赖性速发型超敏反应的口服抑制剂，在大鼠和豚鼠中的生物学活性与DSCG相似。
