Gastric and duodenal anti-ulcer activity of SKF 38393, a dopamine D1-receptor agonist in rats.
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.
Desai
J K
JK
Department of Pharmacology, L.M. College of Pharmacy, Navrangpura, Ahmedabad, India.
Goyal
R K
RK
Parmar
N S
NS
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003543:Cysteamine; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004381:Duodenal Ulcer / Q000188:drug therapy*; D005260:Female; D007101:Immersion; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D013276:Stomach Ulcer / Q000188:drug therapy*
D000897:Anti-Ulcer Agents; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D003543:Cysteamine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine