新的磷酸二酯酶3抑制剂NT-702（盐酸帕罗格列，NM-702）通过支气管扩张和抗炎作用抑制豚鼠哮喘
2009/09/17
本实验在豚鼠中研究新的选择性磷酸二酯酶3抑制剂NT-702 （盐酸帕罗格列, NM-702, 4-溴-6-[3-(4-氯苯) 丙氧基]-5-[(吡啶-3-甲基) 氨基] 哒嗪-3(2H)-盐酸）对哮喘反应的作用。
在前列腺素E2处理的豚鼠气管平滑肌细胞中，1x10-7M的NT-702能增加环磷酸腺苷的含量。白三烯（LT）D4和组胺诱导的离体豚鼠平滑肌环的收缩能被NT-702所抑制，EC(50)值分别为3.2x10-7和2.5x10-7M。体内实验发现，NT-702通过其支气管扩张作用在豚鼠中抑制LTD4诱导的支气管收缩和卵清蛋白诱导的即刻哮喘反应。而且，NT-702也能抑制卵清蛋白诱导的迟发哮喘反应、气道高反应性和支气管肺泡灌洗液内炎症细胞的数量。
上述结果表明，NT-702具有抗炎和支气管扩张作用，可能成为一个有用的，新的治疗支气管哮喘的药物，这是一类新药物，同时具有支气管扩张和抗炎作用。
（陈欣 审校）
Hori M, Iwama T, Asakura Y, et al.
Eur J Pharmacol. 2009 Jul 17. [Epub ahead of print]
NT-702 (parogrelil hydrochloride, NM-702), a novel and potent phosphodiesterase 3 inhibitor, suppress the asthmatic response in guinea pigs, with both bronchodilating and anti-inflammatory effects
Department of Pharmacology, Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Yoshino-cho, Kita-ku Saitama-shi, Saitama 331-9530, Japan.
We evaluated the effects of NT-702 (parogrelil hydrochloride, NM-702, 4-bromo-6-[3-(4-chlorophenyl) propoxy]-5-[(pyridine-3-ylmethyl) amino] pyridazin-3(2H)-one hydrochloride), a selective phosphodiesterase 3 inhibitor, on the asthmatic response in guinea pigs. NT-702 at a concentration of 1x10(-7)M elevated the cyclic adenosine monophosphate content in prostaglandin E(2)-treated guinea pig tracheal smooth muscle cells. Leukotriene (LT) D(4)- and histamine-induced contraction of isolated guinea pig tracheal strips was inhibited by NT-702, with EC(50) values of 3.2x10(-7) and 2.5x10(-7)M, respectively. In an in vivo study, NT-702 suppressed LTD(4)-induced bronchoconstriction and the ovalbumin-induced immediate asthmatic response in guinea pigs through its bronchodilating effect. Furthermore, NT-702 also suppressed the ovalbumin-induced late asthmatic response, airway hyperresponsiveness, and the accumulation of inflammatory cells in the bronchoalveolar lavage fluid. These results suggest that NT-702 has an anti-inflammatory effect as well as a bronchodilating effect and might be useful as a novel potent therapeutic agent for the treatment of bronchial asthma, a new type of agent with both a bronchodilating and an anti-inflammatory effect.
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治疗改善哮喘的长期预后－12年随访研究
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白三烯受体拮抗剂及合成抑制剂治疗哮喘的疗效
