Protective Action of Omeprazole, a Benzimidazole Derivative, on Gastric Mucosal Damage by Aspirin and Ethanol in Rats

Konturek, S J; Brzozowski, Tomasz; Radecki, T

doi:10.1159/000198946

Cited by 72 publications

(32 citation statements)

References 4 publications

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“…In addition, FRG-8813 also proved to be effective in preventing the lesion formation even when the rats were pretreated with omeprazole (30 mg/kg, s.c.) at the dose required to suppress 2-DG-stimulated acid secretion by about 90010. In contrast, the gastroprotective effect of oral omeprazole used as a reference drug was completely attenuated by the same treatment, and this result is consistent with the previous reports (18,19). Since omeprazole is readily degraded by acidic pH (20), the degraded compounds produced in the gastric juice of the lumen are considered to exert the gastroprotective effect by a local action from the luminal side.…”

Section: Studies Of the Gastroprotective Mechanisms Of Frg-8813supporting

confidence: 89%

Gastroprotective Activity of FRG-8813, a Novel Histamine H2-Receptor Antagonist, in Rats

Onodera

Shibata

Tanaka

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-FRG-8813 ((±)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2-pyridyl]oxy-(Z)-2-butenyl]acetamide) is a novel histamine H2-receptor antagonist with gastric antisecretory and gastroprotective activities. The present study was designed to investigate the property of gastroprotective action. The oral ED50 values for inhibition of mucosal lesions against 1076 NH3-, 60% ethanol in 0.15 N HCl-, 100% ethanol-, 0.6 N HCl-and sodium taurocholate in 0.4 N HCl-induced damage were 3.3, 11.1, 14.9, 23.3 and 23.1 mg/kg, respectively. FRG-8813 was gastroprotective despite pretreatment with omeprazole, suggesting that the protective effect is independent of its antisecretory activity. It is unlikely that FRG-8813 works as a mild irritant because it showed a gastroprotective effect after intraperitoneal injection, but oral administration itself did not influence the rat gastric mucosa. Although pretreatment with indomethacin or N-ethylmaleimide did not affect the gastroprotection of FRG-8813, chemical deafferentation induced by capsaicin abolished the gastroprotection.Furthermore, prior administration of tetrodotoxin, the calcitonin generelated peptide (CGRP) antagonist hCGRP8_37 or N~-nitro-L-arginine attenuated the gastroprotection of FRG-8813 as well as that of capsaicin. In contrast to capsaicin, repeated administration of FRG-8813 neither enhanced the susceptibility of the mucosa to damage nor affected the gastroprotective action of short-term treatment. In conclusion, these results suggest that FRG-8813 has gastroprotective activity independently of acid antisecretory activity and that capsaicin-sensitive nerves may be partially or fully involved in the gastroprotective mechanisms of FRG-8813. Keywords:FRG-8813, Gastroprotection, Histamine H2-receptor antagonist, Capsaicin-sensitive nerve, Antiulcer drug Successful peptic ulcer therapy depends on the restoration of the compromised integrity of the gastroduodenal mucosa by either reducing the aggressive factors or enhancing the defensive process in the mucosa. This has been mainly accomplished by reducing intraluminal acid with an histamine H2-receptor antagonist for more than 10 years. The histamine H2-receptor antagonists are among the most frequently employed drugs worldwide, and their leading position can be explained by their proven high antisecretory potency (1, 2). However, numerous reports showed that the incidence of ulcer relapse after discontinuation of the histamine H2-receptor antagonist reaches the same level as that in patients receiving a placebo (3 -5). From these viewpoints, further improvement in ulcer therapy, with regard to quality of ulcer healing and/or ulcer relapse, might be achieved if the agent could enhance the mucosal defensive capacity in addition to decreasing gastric acid secretion.The property of agents that protect the gastric mucosa against necrotizing agents such as ethanol was defined as so-called "cytoprotection"by Robert et al. (6). Subsequent observations demonstrated that although the gastric cells localized deep in the mu...

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Section: Studies Of the Gastroprotective Mechanisms Of Frg-8813supporting

confidence: 89%

Gastroprotective Activity of FRG-8813, a Novel Histamine H2-Receptor Antagonist, in Rats

Onodera

Shibata

Tanaka

et al. 1995

Japanese Journal of Pharmacology

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“…Omeprazole, a proton-pump inhibitor, prevents dam age caused by necrotizing agents such as absolute ethanol and 35010 NaCl in rat gastric mucosa (1,2). This effect is also found in other proton-pump inhibitors (3)(4)(5).…”

mentioning

confidence: 77%

“…The mechanism of the cytoprotection is, however, not known. This effect of proton-pump inhibitors is observed only when the drugs are given intragastrically (2)(3)(4). So, pro ton-pump inhibitors might need to come in contact with gastric contents, especially gastric acid, to induce cyto protection.…”

mentioning

confidence: 99%

Intrathecal Noradrenaline Facilitates and Inhibits the Flexor Reflex Mediated by Group II Afferent Fibers via α1- and α2-Receptors, Respectively

Fukuda

Higuchi

Koike

et al. 1993

Japanese Journal of Pharmacology

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“…Konturek et al (20) has reported that omeprazole has no effect on the biosynthesis of gastric mucosal PGI2. Moreover, omeprazole has been reported to have no effects on the biosynthesis of PG in human tissue culture (21) or in isolated gastric mucosal cells from guinea pigs (22).…”

Section: Discussionmentioning

confidence: 99%

Effects of NC-1300-0-3 on Gastric Mucus Secretion and Prostaglandin Release in Rats

Matsukura

Masuda

Uchida

et al. 1994

Japanese Journal of Pharmacology

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Protective Action of Omeprazole, a Benzimidazole Derivative, on Gastric Mucosal Damage by Aspirin and Ethanol in Rats

Cited by 72 publications

References 4 publications

Gastroprotective Activity of FRG-8813, a Novel Histamine H2-Receptor Antagonist, in Rats

Gastroprotective Activity of FRG-8813, a Novel Histamine H2-Receptor Antagonist, in Rats

Intrathecal Noradrenaline Facilitates and Inhibits the Flexor Reflex Mediated by Group II Afferent Fibers via α1- and α2-Receptors, Respectively

Effects of NC-1300-0-3 on Gastric Mucus Secretion and Prostaglandin Release in Rats

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