Gaginella T S, Bertko R J, Müller R K, Gallo-Torres H, Sullivan A C
J Pharmacol Exp Ther. 1985 Jan;232(1):208-13.
The synthetic trimethyl prostanoid Ro 22-6923 was studied for its effects on histamine-stimulated gastric acid secretion in Heidenhain pouch dogs. The prostanoid (at a p.o. dose as low as 0.05 mg/kg) produced significant inhibition of gastric acid secretion induced by 12 micrograms/kg/h of histamine for 5 h. A dose of 0.5 mg/kg p.o. produced a significant antisecretory effect within 45 min that lasted for 8.5 h. Cimetidine (5 mg/kg p.o.) produced an inhibitory effect on acid output equivalent to the 0.5-mg/kg dose of Ro 22-6923, but the duration of the cimetidine effect was less than 6 h. Administration of Ro 22-6923 i.v. (0.25 mg/kg) inhibited acid output for longer than 8 h. Against a 25-micrograms/kg/h histamine challenge, Ro 22-6923 (0.5 and 1.0 mg/kg) inhibited acid output to an equal degree but for a longer duration than cimetidine (5 mg/kg). Pepsin output was totally inhibited by 0.5 mg/kg of Ro 22-6923, whereas 5 mg/kg of cimetidine inhibited pepsin output by approximately 60%. Pepsin activity in the gastric juice was reduced by Ro 22-6923 and was increased by cimetidine. Blood flow, as estimated by the aminopyrine clearance technique, was reduced slightly by Ro 22-6923 and cimetidine. However, the ratio of clearance to acid secretory rate increased with both compounds, suggesting a direct effect of Ro 22-6923 and cimetidine on acid secretion at the parietal cell level. The results suggest that Ro 22-6923 may be a useful therapeutic agent for peptic ulcer disease in humans.
研究了合成的三甲基前列腺素Ro 22 - 6923对海登海因小胃犬组胺刺激胃酸分泌的影响。该前列腺素（口服剂量低至0.05 mg/kg）对12微克/千克/小时组胺诱导的胃酸分泌产生显著抑制作用，持续5小时。口服剂量为0.5 mg/kg时，在45分钟内产生显著的抗分泌作用，持续8.5小时。西咪替丁（口服5 mg/kg）对胃酸分泌的抑制作用与0.5 mg/kg剂量的Ro 22 - 6923相当，但西咪替丁作用的持续时间小于6小时。静脉注射Ro 22 - 6923（0.25 mg/kg）抑制胃酸分泌的时间超过8小时。对于25微克/千克/小时组胺刺激，Ro 22 - 6923（0.5和1.0 mg/kg）抑制胃酸分泌的程度与西咪替丁（5 mg/kg）相当，但持续时间更长。0.5 mg/kg的Ro 22 - 6923可完全抑制胃蛋白酶分泌，而5 mg/kg的西咪替丁可抑制胃蛋白酶分泌约60%。Ro 22 - 6923可降低胃液中的胃蛋白酶活性，而西咪替丁则使其升高。用氨基比林清除技术估算的血流量，Ro 22 - 6923和西咪替丁均使其略有降低。然而，两种化合物的清除率与酸分泌率之比均升高，表明Ro 22 - 6923和西咪替丁在壁细胞水平对胃酸分泌有直接作用。结果表明，Ro 22 - 6923可能是治疗人类消化性溃疡病的有用药物。
