Johnson H G, Stout B K
Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, Mich.
Int Arch Allergy Appl Immunol. 1988;87(2):204-7. doi: 10.1159/000234673.
The IgE-mediated hypersensitivity to Ascaris antigen in reactor rhesus primates was used to assess the pharmacologic profile of U-66,858 (1-acetoxy-2-n-butyl-4-methoxy-naphthalene). When the compound was given by the oral route, it showed dose-related inhibition of resistance (RL) and compliance (Cdyn) changes. When the compound was given by the aerosol route, it showed dose independent inhibition. In 15 animals, aerosols (52 +/- 32 to 53 +/- 10% for RL, p = 0.05 and 45 +/- 19 to 28 +/- 19% Cdyn inhibitions, p = 0.05) for 5.0-0.1% aerosol. By the oral route, inhibition was seen at 1-4 h following administration. In 5 animals, oral doses of 10 and 5 mg/kg inhibited (RL by 98 +/- 2 to 78 +/- 1.5%, p = 0.01 and Cdyn by 75 +/- 17 to 60.9 +/- 9.1%, p = 0.05) by 10 and 5 mg/kg U-66,858, respectively. The in vivo demonstration of inhibition of pulmonary bronchoconstriction by this compound, in a model known to be leukotriene sensitive, coupled with its potent in vitro inhibition of 5-lipoxygenase enzymes, suggests this compound may be of use in 5-lypoxygenase-mediated models of asthma.
利用反应性恒河猴对蛔虫抗原的IgE介导超敏反应来评估U-66,858（1-乙酰氧基-2-正丁基-4-甲氧基萘）的药理学特征。当通过口服途径给予该化合物时，它显示出与剂量相关的对阻力（RL）和顺应性（Cdyn）变化的抑制作用。当通过气雾剂途径给予该化合物时，它显示出与剂量无关的抑制作用。在15只动物中，气雾剂（RL为52±32%至53±10%，p = 0.05；Cdyn抑制率为45±19%至28±19%，p = 0.05）用于5.0 - 0.1%的气雾剂。通过口服途径，在给药后1 - 4小时观察到抑制作用。在5只动物中，10和5 mg/kg的口服剂量分别使U-66,858对RL的抑制率为98±2%至78±1.5%（p = 0.01），对Cdyn的抑制率为75±17%至60.9±9.1%（p = 0.05）。在一个已知对白三烯敏感的模型中，该化合物在体内对肺支气管收缩的抑制作用，再加上其在体外对5-脂氧合酶的强效抑制作用，表明该化合物可能用于5-脂氧合酶介导的哮喘模型。
