Rossoni G, Omini C, Folco G C, Vigano T, Brunelli G, Berti F
Arch Int Pharmacodyn Ther. 1984 Mar;268(1):128-40.
The bronchodilating activity of mequitazine (MQ) (10-[3- quinuclidynilmethyl ]-phenothiazine) has been investigated in the guinea-pig using various spasmogens such as acetylcholine, histamine and leukotriene-C4 (LTC4). Mequitazine showed a potent protecting activity versus bronchoconstriction induced by the above agonists and was also able to prevent their capacity to trigger activation of arachidonic acid metabolism and preferential formation of TXA2. The results obtained with the "in vivo" experiments correlate well with those obtained "in vitro" using guinea-pig perfused lungs, where LTC4 and histamine stimulate TXA2 formation and release in the pulmonary effluent. MQ demonstrated its efficacy in protecting passively sensitized guinea-pigs from antigen challenge; this protection is accompanied by a substantial reduction of circulating TXA2. The bronchodilating and antiallergic activity of MQ is likely due to a direct control of histamine and muscarinic receptors and to a diminished bioamplification via eicosanoid activation. In addition, the capacity of MQ to counteract the "in vitro" and "in vivo" effects of LTC4 adds interest to its therapeutic potential.
已在豚鼠中使用多种致痉剂（如乙酰胆碱、组胺和白三烯-C4（LTC4））研究了美喹他嗪（MQ，10-[3-喹核啶基甲基]-吩噻嗪）的支气管扩张活性。美喹他嗪对上述激动剂诱导的支气管收缩表现出强大的保护活性，并且还能够阻止它们触发花生四烯酸代谢激活和TXA2优先形成的能力。“体内”实验获得的结果与使用豚鼠灌注肺进行的“体外”实验结果密切相关，在豚鼠灌注肺实验中，LTC4和组胺刺激肺流出物中TXA2的形成和释放。MQ证明了其在保护被动致敏豚鼠免受抗原攻击方面的功效；这种保护伴随着循环TXA2的大幅减少。MQ的支气管扩张和抗过敏活性可能归因于对组胺和毒蕈碱受体的直接控制以及通过类花生酸激活减少生物放大作用。此外，MQ对抗LTC4“体外”和“体内”作用的能力增加了其治疗潜力的吸引力。
