Desai J K, Goyal R K, Parmar N S
Department of Pharmacology, L.M. College of Pharmacy, Navrangpura, Ahmedabad, India.
J Pharm Pharmacol. 1995 Sep;47(9):734-8. doi: 10.1111/j.2042-7158.1995.tb06733.x.
The effect of SKF 38393 (1-phenyl-7,8-diol-2,3,4,5-tetrahydro-1H-3-benzazepine), a specific dopamine D1-receptor agonist, was studied on pylorus-ligation and water immersion plus restraint stress-induced gastric ulcers, and cysteamine-induced duodenal ulcers in rats. Repeated administration of SKF 38393 (5 and 10 mg kg-1, p.o.) for six days was found to be effective in the prevention of gastric ulceration induced by water immersion plus restraint stress in rats. In 19-h pylorus-ligated rats, repeated treatment with SKF 38393 showed a significant reduction in the number and severity of ulcers. SKF 38393 did not alter the total gastric-mucosal carbohydrates:protein ratio; however, the gastric content volume and the free and total acidity were significantly reduced. In cysteamine-induced duodenal ulcers, the treatment with SKF 38393 for 6 days prevented the duodenal lesions. Our data suggests the involvement of dopamine D1 receptors in the anti-ulcer activity of SKF 38393, which could be largely attributed to its anti-secretory effect. Its anti-ulcer activity against water immersion plus restraint, also points towards a central mode of action, but its failure to alter the carbohydrate:protein ratio rules out any protective effect through the strengthening of the gastric mucosal barrier.
研究了特异性多巴胺D1受体激动剂SKF 38393（1-苯基-7,8-二醇-2,3,4,5-四氢-1H-3-苯并氮杂卓）对大鼠幽门结扎、水浸加束缚应激诱导的胃溃疡以及半胱胺诱导的十二指肠溃疡的影响。发现连续六天口服给予SKF 38393（5和10 mg/kg）可有效预防大鼠水浸加束缚应激诱导的胃溃疡。在幽门结扎19小时的大鼠中，重复给予SKF 38393可显著减少溃疡的数量和严重程度。SKF 38393不会改变胃黏膜总碳水化合物与蛋白质的比例；然而，胃内容物体积以及游离酸度和总酸度均显著降低。在半胱胺诱导的十二指肠溃疡中，给予SKF 38393治疗6天可预防十二指肠损伤。我们的数据表明多巴胺D1受体参与了SKF 38393的抗溃疡活性，这在很大程度上可能归因于其抗分泌作用。其对水浸加束缚应激的抗溃疡活性也表明其作用方式可能是中枢性的，但其未能改变碳水化合物与蛋白质的比例排除了通过加强胃黏膜屏障产生任何保护作用的可能性。
