Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients
Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients
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DOI：
10.1183/09031936.03.00101902
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发表时间：
2004-01-01
影响因子：
24.3
通讯作者：
Pauwels, RA
中科院分区：
文献类型：
--
作者：
Joos, GF;Vincken, W;Pauwels, RA
吸入神经激肽A（NKA）可引起哮喘患者支气管收缩。在体外，速激肽NK 1和NK 2受体都可以介导气道收缩。在这项研究中，作者检测了单剂量速激肽NK 1/NK 2双重受体拮抗剂DNK 333对哮喘患者NKA诱导的支气管收缩的影响。共有19名轻度哮喘男性成人完成了一项随机、双盲、安慰剂对照的交叉试验。增加NKA的浓度（3.3 × 10（-9）至1.0 × 10（-6）mol（.）在单次口服DNK 333（100 mg）或安慰剂后，以1和10 h间隔吸入DNK 333（100 mL（-1））。NKA在1秒内引起用力呼气量下降20%的平均log（10）激发浓度为-5.6 log（10）mol（.）在DNK 333处理后1 h，-6.8 log（10）mol（.）mL（-1）。这相当于4.08倍剂量的差异，在治疗后10 h降低到0.90倍剂量的差异。本报告中显示的结果表明，DNK 333阻断哮喘患者神经激肽A诱导的支气管收缩。
Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK1 and NK2 receptors can mediate airway contraction. In this study the authors examined the effects of a single dose of the dual tachykinin NK1/NK2 receptor antagonist, DNK333, on NKA-induced bronchoconstriction in asthma.A total of 19 male adults with mild asthma completed a randomised, double-blind, placebo-controlled crossover trial. Increasing concentrations of NKA (3.3 x 10(-9) to 1.0 x 10(-6) mol(.)mL(-1)) were inhaled at 1 and 10 h intervals after a single oral dosing with either DNK333 (100 mg) or a placebo.It was observed that DNK333 did not affect baseline lung function but did protect against NKA-induced bronchoconstriction in those patients. The mean log(10) provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was -5.6 log(10) mol(.)mL(-1) at 1 h after DNK333 treatment and -6.8 log(10) mol(.)mL(-1) after placebo. This was equivalent to a difference of 4.08 doubling doses, which decreased to a difference of 0.90 doubling doses 10 h after treatment.The results shown in this report indicate that DNK333 blocks neurokinin A-induced bronchoconstriction in patients with asthma.