Subissi A, Criscuoli M, Renzetti A R
Eur J Pharmacol. 1986 Jul 15;126(1-2):81-9. doi: 10.1016/0014-2999(86)90741-7.
LG 30435, a new quaternary derivative of the H1-histamine antagonist mequitazine, was evaluated against bronchospasm induced by different agonists. This compound inhibited equipotently methacholine- and histamine-induced contractions of isolated guinea-pig trachea. When administered to guinea-pig by the i.v. and/or the aerosol route, LG 30435 inhibited dose dependently the bronchospasm induced by acetylcholine and histamine and to a lesser degree that induced by 5-hydroxytryptamine and LTD4. When compared to that of mequitazine, its potency was higher in each case, up to 500-fold when tested in vitro against methacholine. LG 30435 also counteracted antigen-induced bronchospasm both in passively sensitized guinea-pigs and in actively sensitized rats. This compound had a rapid onset of action and an adequate duration after aerosol administration. It was poorly absorbed both by the oral and the aerosol routes and it did not appear to penetrate the blood-brain barrier. These results show that LG 30435 is a new aerosol bronchodilator agent, which, due to its multiple pharmacodynamic actions and to its suitable pharmacokinetics, is potentially useful in the therapy of obstructive airways disease.
LG 30435是H1组胺拮抗剂美喹他嗪的一种新型季铵衍生物，针对不同激动剂诱导的支气管痉挛进行了评估。该化合物对豚鼠离体气管中乙酰甲胆碱和组胺诱导的收缩具有同等程度的抑制作用。当通过静脉注射和/或气雾剂途径给予豚鼠时，LG 30435剂量依赖性地抑制乙酰胆碱和组胺诱导的支气管痉挛，对5-羟色胺和白三烯D4诱导的支气管痉挛的抑制作用较小。与美喹他嗪相比，在每种情况下其效力都更高，在体外针对乙酰甲胆碱测试时高达500倍。LG 30435还能对抗被动致敏豚鼠和主动致敏大鼠中抗原诱导的支气管痉挛。该化合物气雾剂给药后起效迅速，作用持续时间适中。口服和气雾剂途径的吸收都很差，且似乎不会穿透血脑屏障。这些结果表明，LG 30435是一种新型气雾剂支气管扩张剂，由于其多种药效学作用和合适的药代动力学，在阻塞性气道疾病的治疗中可能具有应用价值。
