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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effects of a new sigma ligand, JO 1784, on cysteamine ulcers and duodenal alkaline secretion in rats.

BACKGROUND: The ulceroprotective effects of JO 1784 [(+)-N-cyclopropyl-methyl-N-methyl-1,4-diphenyl-1-ethyl-but-3-en-1-yl amine, hydrochloride], a new specific and highly selective sigma ligand, were examined in rats. METHODS: Different models of gastric ulcers (4-hour restraint stress, aspirin, ethanol, and taurocholate) and cysteamine-induced duodenal ulcers were used. The gastric acid secretion (4-hour Shay rat preparation) and the duodenal bicarbonate secretion were also studied. RESULTS: JO 1784 elicited a potent protection against duodenal ulcers but had a weaker protective effect on any of the gastric ulceration models tested. It displayed no gastric antisecretory activity but induced a dose-dependent stimulation of duodenal bicarbonate secretion. Haloperidol, hexamethonium, tetrodotoxin, bivagotomy (but not atropine), and the intravenous but not intracerebroventricular administration of devazepide, a cholecystokinin A antagonist, inhibited the stimulatory effect of JO 1784. CONCLUSION: These results show that JO 1784, a selective sigma ligand, is a potent protector of the duodenal mucosa. This activity may be related to its stimulating effect on bicarbonate secretion, which is driven through a complex nervous mechanism involving muscarinic synapses, vagal afferent fibers, and peripheral cholecystokinin receptors. This drug might open a new specific way in the treatment of duodenal ulcers.[1]

References

  1. Effects of a new sigma ligand, JO 1784, on cysteamine ulcers and duodenal alkaline secretion in rats. Pascaud, X.B., Chovet, M., Soulard, P., Chevalier, E., Roze, C., Junien, J.L. Gastroenterology (1993) [Pubmed]
 
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