Affiliation:
1. Department of Pharmacology, Janssen Pharmaceutica, Research Laboratoria, B-2340 Beerse, Belgium
Abstract
Abstract
Forty-four non-steroidal anti-inflammatory compounds were tested for possible effects on castor oil-induced diarrhoea in rats. A small but significant delay of intestinal evacuations was found with all compounds. Quantitatively, the oral doses required to delay diarrhoea beyond the first hour after castor oil challenge reflected the acute anti-inflammatory potency of the tested compounds. Qualitatively, the evolution of the effective doses with increasing delay was linear for potent inhibitors of prostaglandin biosynthesis. The evolution for less potent compounds was markedly different and suggested the earlier occurrence of nonspecific drug effects. Suprofen, the most potent of the series of compounds, produced the 1 h delay at an oral dose of 1·11 mg kg−1; the ED50 increased linearly to 115 mg kg−1 for a 4 h delay. Compared with other compounds the activity pattern of suprofen was consistent with that of a very potent, short-acting inhibitor of prostaglandin biosynthesis, which maintains its specific action over a wide dose range. It is concluded that delay of castor oil-induced diarrhoea in rats allows a detailed characterization of aspirin-like compounds, and that inhibition of prostaglandin biosynthesis is insufficient to suppress the intestinal effects of the oil.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
217 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献