Peripheral biological activity of SR 27897: a new potent non-peptide antagonist of CCKA receptors

Eur J Pharmacol. 1993 Feb 23;232(1):13-9. doi: 10.1016/0014-2999(93)90722-t.


SR 27897 is a new non-peptide antagonist of CCKA receptors: 1-[[2-(4-(2-chlorophenyl)thiazol-2-yl)aminocarbonyl] indolyl] acetic acid. This compound is a potent ligand for CCKA binding sites (rat pancreatic membranes, Ki = 0.2 nM) and is highly selective (CCKB and gastrin/CCKA IC50 ratios of 800 and 5000 respectively). In vitro, it is a competitive antagonist of cholecystokinin (CCK)-stimulated amylase release in isolated rat pancreatic acini (pA2 = 7.50) and of CCK-induced guinea pig gall bladder contractions (pA2 = 9.57). In in vivo gastrointestinal models, SR 27897 confirmed the potency obtained in vitro: at 1 mg/kg (i.v.) it completely reversed the CCK-induced amylase secretion, at 3 micrograms/kg (p.o.) it antagonized by 50% the CCK-induced inhibition of gastric emptying of a charcoal meal in mice, and 72 micrograms/kg (p.o.) was the median effective dose for inhibiting CCK-induced gall bladder emptying in mice. SR 27897 was also very active (ED50 = 27 micrograms/kg p.o.) in the gall bladder emptying protocol with egg yolk as an inducer of endogenous CCK release. SR 27897 had a long-lasting action in all the experiments, with no differences between oral and intravenous routes of administration. SR 27897 was more or less effective than L-364,718, depending on the model and the species. Both compounds increased the gall bladder volume of fasting mice, but the effect of SR 27897 was 10 times lower than that of L-364,718. In summary, SR 27897 is a selective antagonist of CCKA receptors, is highly potent in animal models whatever the route of administration and has a long duration of action.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Amylases / drug effects
  • Animals
  • Benzodiazepinones / pharmacology
  • Binding, Competitive
  • Cholecystokinin / antagonists & inhibitors
  • Cholecystokinin / metabolism
  • Devazepide
  • Dose-Response Relationship, Drug
  • Female
  • Gallbladder / drug effects
  • Gastric Emptying / drug effects
  • Gastrins / drug effects
  • Guinea Pigs
  • In Vitro Techniques
  • Indoleacetic Acids / pharmacology*
  • Injections, Intravenous
  • Male
  • Mice
  • Pancreas / drug effects
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Cholecystokinin / antagonists & inhibitors*
  • Stomach / drug effects
  • Thiazoles / pharmacology*


  • Benzodiazepinones
  • Gastrins
  • Indoleacetic Acids
  • Receptors, Cholecystokinin
  • Thiazoles
  • SR 27897
  • Cholecystokinin
  • Amylases
  • Devazepide