Propionitrile-induced duodenal ulcers

Recent data in our laboratories indicated the possible involvement of central and peripheral dopamine binding sites in the pathogenesis of duodenal ulceration. Structure activity studies with duodenal ulcerogens implicated dopamine as a putative mediator and/or modulator in duodenal ulceration. Using the cysteamine- or propionitrile-induced duodenal ulcer model in rats, we found that dopamine agonists (e.g., bromocriptine, lergotrile,... 

TABLE I. Effect of Bromocriptine or Lergotrile on Propionitrile-Induced Duodenal Ulcers in the Rat... 

The lesion in the duodenum developed even more rapidly (e.g., perforation in 24 h after a single dose) and more predictably than with propionitrile. Acetanilide was the first aryl chemical noted to cause duodenal ulcer ( 18). Subsequently, 3,4-toluenediamine ( ) and 3,4-toluenedithiol (20) were also shown to induce duodenal ulcers and occasionally adrenal necrosis in rats. 

The duodenal ulcerogenic action of propionitrile and cysteamine was confirmed and extended by several authors (J, 8, 25-32). The model, especially the rapidly developing cysteamine-induced duodenal ulcer, was actually introduced in several laboratories to routinely test drugs for anti-ulcer activity (7.8,27.33). The cysteamine model, a simple, fast, and inexpensive procedure, became especially useful after a chronic form of duodenal ulcer was developed ( ) and similarities between the model and human duodenal ulceration were noted (7-10). 

The actions of these drugs are not specific to cysteamine since the intensity of propionitrile-induced acute duodenal ulcers was also significantly diminished after pretreatment with bromocriptine or lergotrile (Table I). 

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