Hoymann H G, Heinrich U, Beume R, Kilian U
Fraunhofer Institute of Toxicology and Aerosol Research, Hannover, Germany.
Exp Lung Res. 1994 May-Jun;20(3):235-50. doi: 10.3109/01902149409064385.
Zardaverine (Byk Gulden, Konstanz, Germany) is a new selective phosphodiesterase (PDE) III/IV inhibitor. The bronchodilating and bronchoprotective potency of zardaverine and the nonselective PDE inhibitor theophylline was compared by measuring typical spontaneous and forced respiratory function parameters in anesthetized female Wistar rats using whole-body plethysmography. Zardaverine (3, 10, 30 mumol/kg) and theophylline (30, 100, 300 mumol/kg), respectively, were given orally in 4% Methocel/0.9% saline solution 20 min before measurement. One week before treatment, control measurements were performed in the same animals after administration of the vehicle. When spontaneously breathing, the 30 mumol/kg zardaverine- (300 mumol/kg theophylline-) treated animals showed significant changes: a 23% (14% ns) decrease in lung resistance and a 43% (25%) increase in dynamic compliance. These changes can be interpreted as an indication of bronchodilation, since quasistatic lung compliance was unchanged. In the acetylcholine challenge test, treatment with only 10 mumol/kg zardaverine (but 300 mumol/kg theophylline) revealed significant changes compared to control measurement: a 37% (28%) lower resistance and 85% (44%) higher compliance. It has been determined that zardaverine is more than 30 times as potent as theophylline in inhibiting acetylcholine-induced bronchospasms, which is also supported by forced expiratory flow data.
扎达维林（德国康斯坦茨的拜耳古登公司）是一种新型选择性磷酸二酯酶（PDE）III/IV抑制剂。通过使用全身容积描记法测量麻醉雌性Wistar大鼠的典型自发和强迫呼吸功能参数，比较了扎达维林与非选择性PDE抑制剂茶碱的支气管扩张和支气管保护效力。在测量前20分钟，分别以4%甲基纤维素/0.9%盐溶液口服给予扎达维林（3、10、30 μmol/kg）和茶碱（30、100、300 μmol/kg）。在治疗前一周，在给予赋形剂后对同一批动物进行对照测量。在自主呼吸时，接受30 μmol/kg扎达维林（300 μmol/kg茶碱）治疗的动物出现了显著变化：肺阻力降低23%（14%无显著性差异），动态顺应性增加43%（25%）。由于准静态肺顺应性未改变，这些变化可解释为支气管扩张的迹象。在乙酰胆碱激发试验中，与对照测量相比，仅用10 μmol/kg扎达维林（但300 μmol/kg茶碱）治疗就显示出显著变化：阻力降低37%（28%），顺应性提高85%（44%）。已确定扎达维林在抑制乙酰胆碱诱导的支气管痉挛方面比茶碱强效30倍以上，这也得到了用力呼气流量数据的支持。
