PubMed · 2563070
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T Badrick, P Hickman. 1989-01-21. Anion gap.. https://doi.org/10.1016/s0140-6736(89)91169-0
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We investigated the effects of omeprazole and Sch 28080, a more specific and a more potent inhibitor of K+,H+-ATPase than omeprazole, in canine 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 synthetic CSF) was added to VCP in group III, after baseline control CSF production had been determined at 15, 30, 45, and 60 min. Comparing the three groups, the mean baseline values for CSF production did not differ significantly. However, the percent decreases in CSF production in the omeprazole treated group were 26 +/- 17 and 24 +/- 13 at 210 and 225 min, which were significantly more than the respective values in the control group. Percent decrease in CSF production in Sch 28080 was not significantly different from that in the control group. We conclude that in the canine model, physiological doses of omeprazole decrease CSF production by about 26%. However, the effect is independent of the K+,H+-ATPase activity, since Sch 28080 which is more potent than omeprazole did not significantly affect CSF production.
In the present paper we tried to test the hypothesis that nonspecific flunitrazepam-membrane interactions are consistent with drug molecules accommodated between lipid molecules, becoming an integral part of the bilayer. We developed a spectrophotometric method to determine FNTZH+ equilibrium dissociation constant and applied it to the study of the acid-base equilibria of this drug in homogeneous media of different polarity. In these conditions, pK decreased with the decrement in the dielectric constant (D) of the media. These results, analyzed under the light of the theory developed by Fernandez and Fromherz (1977; J. Phys. Chem. 81, 1755-1761) let us infer that flunitrazepam is localized a region with D = 60. This D value is lower that Dwater = 78 and higher than D of hydrocarbon chains zone (D = 2-5) and would correspond to D of the region of polar groups. This result is compatible with the hypothesis.
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