The recognition of the role of Helicobacter pylori in the pathogenesis of
peptic ulcer disease has led to renewed interest in
bismuth pharmacology since
bismuth compounds have both anti-Helicobacter pylori and
ulcer healing properties. The precise chemical structure of current
bismuth compounds is not known. This has hindered the development of new and potentially more efficacious formulations. We have created two new compounds, 2-chloro-1,3-dithia-2-bismolane (CDTB) and 1,2-[bis(1,3-dithia-2-bismolane)thio]
ethane (BTBT), with known structure. In a rat model of gastric ulceration, BTBT was comparable to, and CDTB was significantly less effective than
colloidal bismuth subcitrate in healing cryoprobe-induced
ulcers. However, both BTBT and CDTB inhibited H. pylori growth in vitro at concentrations <1/10 that of
colloidal bismuth subcitrate. The effects on
ulcer healing are not mediated by suppression of
acid secretion,
pepsin inhibition, or
prostaglandin production. Since all treated animals received the same amount of elemental
bismuth, it appears that the efficacy of
bismuth compounds varies with compound structure and is not simply dependent on the delivery of
bismuth ion. Because the structure of the novel compounds is known, our understanding of the relationship of
bismuth compound structure and to
biologic activity will increase. In the future it may be possible to design other novel
bismuth compounds with more potent anti-H. pylori and
ulcer healing effects.