Berti F, Daffonchio L, Magni F, Omini C, Rossoni G, Subissi A
Institute of Pharmacological Sciences, University of Milan, Italy.
Eur Respir J. 1989 Oct;2(9):868-73.
LG 30435 is a new quarternary phenothiazine derivative with H1-antihistaminic and antimuscarinic properties. The ability of LG 30435 to prevent changes in respiratory mechanics, induced by different mediators and the immunological reaction, was monitored together with biological and radioimmunological determination of circulating thromboxane-A2 (TxA2) in anaesthetized guinea-pigs. LG 30435 dose-dependently reduces the bronchoconstriction and TxA2 generation caused by different stimuli such as histamine, acetylcholine, leukotriene C4 (LTC4) and PAF-acether. In addition i.v. and aerosol administration of LG 30435 causes a dose-dependent reduction of the increase in airway resistance and TxA2 generation induced by ovalbumin challenge in actively sensitized animals. LG 30435 infused at different concentrations through the isolated guinea-pig lungs inhibits the TxB2 generation caused by different anaphylactic mediators, but not by arachidonic acid. These data, which further substantiate the bronchodilator activity of LG 30435 against a variety of stimuli and demonstrate its protective properties on lung anaphylaxis, suggest that this compound has a potential therapeutic value in the treatment of asthma.
LG 30435是一种新型的具有H1抗组胺和抗毒蕈碱特性的季铵类吩噻嗪衍生物。在麻醉的豚鼠中，监测LG 30435预防由不同介质和免疫反应诱导的呼吸力学变化的能力，同时对循环血栓素A2（TxA2）进行生物学和放射免疫测定。LG 30435剂量依赖性地减少由组胺、乙酰胆碱、白三烯C4（LTC4）和血小板活化因子（PAF-乙醚）等不同刺激引起的支气管收缩和TxA2生成。此外，静脉注射和气雾剂给药LG 30435可使主动致敏动物在卵清蛋白激发后气道阻力增加和TxA2生成呈剂量依赖性降低。通过分离的豚鼠肺以不同浓度输注LG 30435可抑制由不同过敏介质引起的TxB2生成，但不抑制花生四烯酸引起的TxB2生成。这些数据进一步证实了LG 30435对多种刺激的支气管扩张活性，并证明了其对肺过敏反应的保护特性，表明该化合物在哮喘治疗中具有潜在的治疗价值。
