DIFFERENT EFFECTS OF OMEPRAZOLE AND SCH-28080 ON CANINE CEREBROSPINAL-FLUID PRODUCTION

We investigated the effects of omeprazole and Sch 28080, a more specif ic and a more potent inhibitor of K+,H+-ATPase than omeprazole, in can ine cerebrospinal fluid (CSF) production. CSF production was measured by ventriculocisternal perfusion (VCP) technique in three groups (n=10 in each group) of anesthetized, paralyzed and mechanically ventilated dogs. Group I served as control. Sch 28080 (10(-4) mol/l of synthetic CSF) was added to VCP in group II, and omeprazole (10(-5) mol/l of sy nthetic CSF) was added to VCP in group III, after baseline control CSF production had been determined at 15, 30, 45, and 60 min. Comparing t he three groups, the mean baseline values for CSF production did not d iffer significantly. However, the percent decreases in CSF production in the omeprazole treated group were 26+/-17 and 24+/-13 at 210 and 22 5 min, which were significantly more than the respective values in the control group. Percent decrease in CSF production in Sch 28080 was no t significantly different from that in the control group. We conclude that in the canine model, physiological doses of omeprazole decrease C SF production by about 26%. However, the effect is independent of the Kf,Ht-ATPase activity, since Sch 28080 which is more potent than omepr azole did not significantly affect CSF production.