Gardiner P J, Copas J L, Schneider C, Collier H O
Prostaglandins. 1980 Mar;19(3):349-70. doi: 10.1016/0090-6980(80)90070-2.
2-Decarboxy 2-hydroxymethyl prostaglandin E1 (TR4161) relaxed isolated quinea-pig trachea with about double and relaxed human isolated bronchial muscle with about one half the potency of PGE1. In conscious restrained cats an aerosol of TR4161 was about 100-1000 times less active than PGE1 in inducing tracheobronchial irritation. When given intravenously or by aerosol to the anaesthetised spontaneously breathing guinea-pig, TR4161 was approximately equipotent with PGE1 in inhibiting histamine-induced bronchoconstriction and in reducing basal inherent tone. The onset and duration of the bronchodilator effects of TR4161 administered intravenously, however, were significantly longer than those of PGE1. In conscious quinea-pigs, TR4161 by aerosol was approximately three times more potent than PGE1 in preventing histamine-induced convulsions, whereas only TR4161 was active in this test system when the test drugs were administered orally. These observations indicate that TR4161 might be therapeutically useful as a non-irritant prostaglandin bronchoidilator in conditions of airway obstruction.
2-脱羧基-2-羟甲基前列腺素E1（TR4161）对离体豚鼠气管的舒张作用约为前列腺素E1（PGE1）的两倍，对人离体支气管平滑肌的舒张作用约为PGE1的一半。在清醒拘束的猫中，TR4161气雾剂诱发气管支气管刺激的活性比PGE1低约100 - 1000倍。当静脉注射或雾化给予麻醉状态下自主呼吸的豚鼠时，TR4161在抑制组胺诱导的支气管收缩和降低基础固有张力方面与PGE1大致等效。然而，静脉注射TR4161的支气管舒张作用的起效时间和持续时间明显长于PGE1。在清醒豚鼠中，雾化给予TR4161在预防组胺诱导的惊厥方面比PGE1强约三倍，而当口服给药时，只有TR4161在该测试系统中有活性。这些观察结果表明，在气道阻塞的情况下，TR4161作为一种无刺激性的前列腺素类支气管扩张剂可能具有治疗用途。
