Pauwels R, Van Renterghem D, Van der Straeten M, Johannesson N, Persson C G
J Allergy Clin Immunol. 1985 Oct;76(4):583-90. doi: 10.1016/0091-6749(85)90779-1.
The effect on the allergen-induced immediate and late bronchoconstriction of theophylline and enprofylline (3-propylxanthine), a new xanthine derivative with negligible ability to antagonize adenosine, was studied in nine patients with asthma. The patients were challenged three times at weekly intervals with the same dose of allergen. FEV1 and SGaw were followed up to 6 hours after challenge. The drugs were administered intravenously. Placebo was always administered on the first occasion. Theophylline and enprofylline were administered on test days 2 and 3 with a double-blind, randomized crossover technique. One hour before the allergen challenge, a loading dose was administered during 60 minutes followed by a constant infusion during 6 hours. The loading infusion was 7.2 mg/kg of theophylline and 2.7 mg/kg of enprofylline. The maintenance dose was 74 mg/hr and 71 mg/hr, respectively. Both theophylline and enprofylline caused a minor initial bronchodilatation. Theophylline and enprofylline slightly but significantly attenuated the immediate bronchoconstricting reaction after allergen inhalation. Theophylline and enprofylline had a significant attenuating effect on the late bronchial reaction. The mean plasma level of theophylline was 0, 10.8, 10.5, and 10.5 mg/L at 0, 1, 4, and 7 hours after the start of the loading infusion, respectively. The corresponding mean plasma levels of enprofylline were 0, 2.6, 2.7, and 2.7 mg/L. Theophylline and enprofylline caused headache in one patient. Two patients developed nausea and vomiting during the enprofylline infusion. The present data suggest that adenosine receptor antagonism may not be the main mode of action of xanthines in inhibiting bronchoconstriction after single dose antigen challenge.
在9例哮喘患者中，研究了茶碱和恩丙茶碱（3-丙基黄嘌呤，一种拮抗腺苷能力可忽略不计的新型黄嘌呤衍生物）对变应原诱导的速发和迟发支气管收缩的影响。患者每周接受相同剂量变应原激发3次。激发后对第1秒用力呼气容积（FEV1）和比气道传导率（SGaw）进行长达6小时的随访。药物通过静脉给药。每次激发的首次给药均为安慰剂。在第2天和第3天的试验日，采用双盲、随机交叉技术给予茶碱和恩丙茶碱。在变应原激发前1小时，60分钟内给予负荷剂量，随后6小时持续输注。负荷输注剂量为茶碱7.2mg/kg和恩丙茶碱2.7mg/kg。维持剂量分别为74mg/小时和71mg/小时。茶碱和恩丙茶碱均引起轻微的初始支气管扩张。茶碱和恩丙茶碱可轻微但显著减轻变应原吸入后的速发支气管收缩反应。茶碱和恩丙茶碱对迟发支气管反应有显著的减轻作用。负荷输注开始后0、1、4和7小时，茶碱的平均血浆浓度分别为0、10.8、10.5和10.5mg/L。恩丙茶碱的相应平均血浆浓度分别为0、2.6、2.7和2.7mg/L。茶碱和恩丙茶碱各使1例患者出现头痛。2例患者在恩丙茶碱输注期间出现恶心和呕吐。目前的数据表明，腺苷受体拮抗作用可能不是黄嘌呤类药物在单次剂量抗原激发后抑制支气管收缩的主要作用方式。
