properties of the reversible, K +-competitive inhibitor of the gastric H +/K +)-ATPase, SK&F 97574. II. Pharmacological properties

• Published in: Biochemical pharmacology 1995-11, Vol.50 (10), p.1551-1556
• Main Authors: Parsons, Michael E., Rushant, Beverly, Rasmussen, Tony C., Leach, Colin, Ife, Robert J., Postius, Stefan, Pope, Andrew J.
• Format: Article
• Language: English
• Subjects: anti-secretory; gastric (H +/K +)-ATPase; inhibitor; mechanism; pharmacology
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(95)02021-7

SK&F 97574 [3-Butryl-4-(2-methylamino)-8-(2-hydroxyethoxy) quinoline] is a potent, reversible inhibitor of the gastric (H +/K +)-ATPase. In an anaesthetised lumen-perfused rat preparation, it inhibited pentagastrin-stimulated gastric acid secretion with intravenous and intraduodenal inhibitory ED 50 values of 2.40 μmol/kg and 4.43 μmol/kg, respectively. In the conscious fistula rat model, doses of 10 μmol/kg IV and 25 μmol/kg PO produced mean peak inhibitions of basal acid output of 91% and 97%, respectively. In these experiments, the duration of action of SK&F 97574 was much shorter than that of the covalent (H +/K +)-ATPase inhibitor, omeprazole. In the conscious Heidenhain pouch dog, SK&F 97574 inhibited histamine-stimulated gastric acid secretion after both intravenous and oral administration with ED 50 values of 0.49 μmol/kg and 0.89 μmol/kg, respectively. In this model, duration of action studies showed that significant residual inhibition of acid secretion remained 8 hours after intravenous dosing with SK&F 97574 (producing peak inhibition of 92%). However, 24 hours after oral dosing of SK&F 97574 (10 μmol/kg), no significant inhibition remained. These data indicate that the duration of action of SK&F 97574 is longer than that of the histamine H 2 receptor antagonists such as cimetidine, but shorter than that of covalent (H +/K +)-inhibitors such as omeprazole. Overall, the pharmacological properties of SK&F 97574 suggest that it could be a potentially useful clinical treatment for acid-related diseases.