Wong W S, Rahwan R G, Stephens R L
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus.
Pharmacology. 1990;41(4):215-23. doi: 10.1159/000138721.
Since propyl-methylenedioxyindene (pr-MDI) exhibits significant protective effects against stress-induced ulcers in rats at subcardiovascular doses (10-30 mg/kg, i.p.), the aim of the present study was to explore the effect of this intracellular calcium antagonist on cysteamine-induced duodenal ulcers at the same low doses. Duodenal ulcers were induced in rats with a single dose of cysteamine (425 mg/kg, s.c.), which produced an 80% ulcer incidence within 24 h without affecting gastric acid concentration. Administration of pr-MDI (10 and 30 mg/kg, i.p.) at 0, 6 and 12 h post-cysteamine did not afford protection against ulceration. On the other hand, atropine (10 mg/kg, s.c., administered at 0, 6 and 12 h post-cysteamine) resulted in a 69% inhibition of ulceration, and the antacid Maalox (2 ml, administered p.o. at 0, 2, 4, 6 and 12 h post-cysteamine) completely prevented ulceration. The failure of pr-MDI to protect against duodenal ulceration is discussed in relation to its pharmacological mechanism of action and the pathogenetic mechanism of action of cysteamine.
由于丙基-亚甲二氧基茚(pr-MDI)在低于心血管剂量(10-30毫克/千克,腹腔注射)时对大鼠应激性溃疡具有显著的保护作用,本研究的目的是探讨这种细胞内钙拮抗剂在相同低剂量下对半胱胺诱导的十二指肠溃疡的影响。用单剂量半胱胺(425毫克/千克,皮下注射)诱导大鼠十二指肠溃疡,该剂量在24小时内导致80%的溃疡发生率,且不影响胃酸浓度。在半胱胺注射后0、6和12小时腹腔注射pr-MDI(10和30毫克/千克)并不能预防溃疡形成。另一方面,阿托品(10毫克/千克,皮下注射,在半胱胺注射后0、6和12小时给药)导致溃疡形成抑制率达69%,抗酸剂氢氧化铝镁(2毫升,口服,在半胱胺注射后0、2、4、6和12小时给药)完全预防了溃疡形成。结合pr-MDI的药理作用机制和半胱胺的发病机制,对pr-MDI未能预防十二指肠溃疡形成进行了讨论。