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

Abstract

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.

• Authors: X B Pascaud, M Chovet, P Soulard, E Chevalier, C Roze, J L Junien
• Journal: Gastroenterology (Gastroenterology) Vol. 104 Issue 2 Pg. 427-34 (Feb 1993) ISSN: 0016-5085 [Print] United States
• PMID: 8425684 (Publication Type: Journal Article)

Chemical References

• Bicarbonates
• Cinnamates
• Cyclopropanes
• Guanidines
• Receptors, sigma
• Cysteamine
• 1,3-ditolylguanidine
• igmesine

Topics

• Animals
• Bicarbonates (metabolism)
• Cinnamates (pharmacology)
• Cyclopropanes (pharmacology)
• Cysteamine
• Duodenal Ulcer (prevention & control)
• Duodenum (drug effects, metabolism)
• Gastric Acid (metabolism)
• Guanidines (pharmacology)
• Male
• Rats
• Rats, Sprague-Dawley
• Receptors, sigma (drug effects)
• Stomach Ulcer (prevention & control)