Inatomi N, Satoh H, Maki Y, Hashimoto N, Itoh Z, Omura S
Biology Research Laboratories, Takeda Chemical Industries, Osaka, Japan.
J Pharmacol Exp Ther. 1989 Nov;251(2):707-12.
The effect of an erythromycin derivative, EM-523, on gastrointestinal motility was investigated in conscious dogs and compared with that of motilin cisapride, trimebutine and metoclopramide. In the fasting state, EM-523 given i.v. or i.d. at 3 micrograms/kg or more induced contractions in the stomach that migrated along the small intestine. The pattern of the contractions was very similar to that induced by motilin. In the digestive state, EM-523 increased the amplitude of gastric contractions. Cisapride and metoclopramide increased gastrointestinal motility both in the fasting and digestive states; however, their contractile pattern was different from that of EM-523. Trimebutine did not induce gastric motility in the fasting state but rather decreased gastric motility in the digestive state. The contractions induced by EM-523 and motilin were inhibited by atropine but were not affected by naloxone, suggesting that the cholinergic pathway is important in the exertion of their action. These results indicate that EM-523 mimics motilin in stimulating gastrointestinal motility and that this agent may be useful treat gastrointestinal disorders such as gastric stasis, gastroesophageal reflux, and postoperative ileus, and so forth.
研究了红霉素衍生物EM - 523对清醒犬胃肠道运动的影响,并与胃动素、西沙必利、曲美布汀和甲氧氯普胺进行比较。在禁食状态下,静脉注射或十二指肠内给予3微克/千克及以上剂量的EM - 523可诱发胃收缩,并沿小肠迁移。收缩模式与胃动素诱发的非常相似。在消化状态下,EM - 523增加胃收缩幅度。西沙必利和甲氧氯普胺在禁食和消化状态下均增加胃肠道运动;然而,它们的收缩模式与EM - 523不同。曲美布汀在禁食状态下不诱发胃运动,反而在消化状态下降低胃运动。EM - 523和胃动素诱发的收缩被阿托品抑制,但不受纳洛酮影响,提示胆碱能途径在其作用发挥中起重要作用。这些结果表明,EM - 523在刺激胃肠道运动方面模拟胃动素,该药物可能对治疗胃肠道疾病如胃潴留、胃食管反流和术后肠梗阻等有用。