Effect of a new non-steroidal anti-inflammatory combination of a histamine H2 antagonist and indomethacin on gastroduodenal mucosal membrane in rat.

Abstract

The new non-steroidal anti-inflammatory drug (NSAID), N-(3-[3-(piperidinyl-methyl) phenoxy] propyl)-carbamoyl-methylthio]ethyl 1-(p-chlorobenzoyl) 5-methoxy-2-methyl-3-indolyl-acetate (CP 331, CAS 127966-70-5), a compound with a structure of an ester combining indomethacin (IM) and a histamine H2 antagonist, has been reported to have anti-inflammatory, analgesic and antipyretic effects. However, the influence of CP-331 on the gastroduodenal mucosa was not fully investigated. Therefore this study was undertaken to investigate the effect of CP-331 on the gastroduodenal mucosa membrane in rats. After single oral drug administration, the UD50 value (50% ulcerogenic dose) of CP-331 calculated from the incidence rate of gastric ulcer was higher than 1000 mg/kg; that for IM was 5.2 mg/kg. Moreover it was examined whether CP-331 had a preventive effect on NSAID-induced gastric damage. The results showed that the co-administration of CP-331 10-30 mg/kg prevented significantly the acute gastric mucosal injury caused by IM administration (20 mg/kg). CP-331 with anti-inflammatory activity does not cause gastric injury, moreover, because of its preventing and therapeutic effects on the damage to gastric mucous membrane induced by IM, CP-331 might be useful in the treatment of gastropathy caused by NSAID in clinic.

• Authors: Y Segawa, T Omata, T Abe, N Tsuzuike, Y Itokazu, K Yoshida, I Ueda
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 42 Issue 10 Pg. 1232-5 (Oct 1992) ISSN: 0004-4172 [Print] Germany
• PMID: 1361736 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Histamine H2 Antagonists
• CP 331
• Indomethacin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects, pharmacology)
• Duodenum (drug effects)
• Gastric Acid (metabolism)
• Gastric Mucosa (drug effects, metabolism)
• Histamine H2 Antagonists (adverse effects, pharmacology)
• Indomethacin (adverse effects, analogs & derivatives, pharmacology)
• Intestinal Mucosa (drug effects, metabolism)
• Male
• Membranes (drug effects)
• Rats
• Rats, Wistar