PROPERTIES OF THE REVERSIBLE, K-COMPETITIVE INHIBITOR OF THE GASTRIC (H+()K+)-ATPASE, SK-AND-F-97574 .2. PHARMACOLOGICAL PROPERTIES/

SK&E 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 pentagastr in-stimulated gastric acid secretion with intravenous and intraduodena l inhibitory ED(50) values of 2.40 mu mol/kg and 4.43 mu mol/kg, respe ctively. In the conscious fistula rat model, doses of 10 mu mol/kg IV and 25 mu mol/kg PO produced mean peak inhibitions of basal acid outpu t 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 afte r both intravenous and oral administration with ED(50) values of 0.49 mu mol/kg and 0.89 mu mol/kg, respectively. In this model, duration of action studies showed that significant residual inhibition of acid se cretion remained 8 hours after intravenous dosing with SK&F 97574 (pro ducing peak inhibition of 92%). However, 24 hours after oral dosing of SK&F 97574 (10 mu mol/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, bu t 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 dis eases.