Gastroprotective activity of FRG-8813, a novel histamine H2-receptor antagonist, in rats
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 1% 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 gene-related peptide (CGRP) antagonist hCGRP or NG-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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1995 |
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| Erschienen: |
1995 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:68 |
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| Enthalten in: |
Japanese journal of pharmacology - 68(1995), 2 vom: 01. Juni, Seite 161-73 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Onodera, S [VerfasserIn] |
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| Themen: |
49S4O7ADLC |
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| Anmerkungen: |
Date Completed 22.11.1995 Date Revised 25.07.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM075401959 |
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| 100 | 1 | |a Onodera, S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Gastroprotective activity of FRG-8813, a novel histamine H2-receptor antagonist, in rats |
| 264 | 1 | |c 1995 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 22.11.1995 | ||
| 500 | |a Date Revised 25.07.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 1% 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 gene-related peptide (CGRP) antagonist hCGRP or NG-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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Acetamides |2 NLM | |
| 650 | 7 | |a Anti-Ulcer Agents |2 NLM | |
| 650 | 7 | |a Histamine H2 Antagonists |2 NLM | |
| 650 | 7 | |a Piperidines |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 650 | 7 | |a lafutidine |2 NLM | |
| 650 | 7 | |a 49S4O7ADLC |2 NLM | |
| 650 | 7 | |a Omeprazole |2 NLM | |
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| 700 | 1 | |a Shibata, M |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, M |e verfasserin |4 aut | |
| 700 | 1 | |a Inaba, N |e verfasserin |4 aut | |
| 700 | 1 | |a Yamaura, T |e verfasserin |4 aut | |
| 700 | 1 | |a Ohnishi, H |e verfasserin |4 aut | |
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