Segawa Y, Omata T, Abe T, Tsuzuike N, Itokazu Y, Yoshida K, Ueda I
Department of Pharmacology, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Arzneimittelforschung. 1992 Oct;42(10):1232-5.
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.
新型非甾体抗炎药（NSAID），N-（3-[3-（哌啶基甲基）苯氧基]丙基）-氨基甲酰甲基硫代]乙基 1-（对氯苯甲酰基）5-甲氧基-2-甲基-3-吲哚基乙酸酯（CP 331，CAS 127966-70-5），一种具有将吲哚美辛（IM）和组胺H2拮抗剂结合的酯结构的化合物，已被报道具有抗炎、镇痛和解热作用。然而，CP-331对胃十二指肠黏膜的影响尚未得到充分研究。因此，本研究旨在探讨CP-331对大鼠胃十二指肠黏膜的作用。单次口服给药后，根据胃溃疡发生率计算的CP-331的UD50值（50%致溃疡剂量）高于1000 mg/kg；IM的该值为5.2 mg/kg。此外，还研究了CP-331是否对NSAID诱导的胃损伤有预防作用。结果表明，联合给予10-30 mg/kg的CP-331可显著预防由IM给药（20 mg/kg）引起的急性胃黏膜损伤。具有抗炎活性的CP-331不会引起胃损伤，此外，由于其对IM诱导的胃黏膜损伤具有预防和治疗作用，CP-331在临床上可能对治疗NSAID引起的胃病有用。
