Inhibition of cerebrospinal fluid formation by omeprazole

Omeprazole, a specific inhibitor of H(+)-K(+)-activated ATPase, gave a dose-dependent inhibition of CSF production as determined by cerebroventriculocisternal perfusions in the rabbit. The reduction was 35% when the perfusate concentration of omeprazole was 10(-6) M and 25% after an intravenous dose of 0.2 mg/kg of omeprazole, respectively. A similarly substituted benzimidazol (H178/42) without H(+)-K(+)-ATPase-inhibiting properties did not affect CSF production at a perfusate concentration of 10(-5) M. Omeprazole in a concentration of 2 x 10(-4) M and more caused a significant but variable reduction in total and Na(+)-K(+)-ATPase activity in choroid plexus homogenates. However, in concentrations of 2 x 10(-5) M and less, no effect on total or Na(+)-K(+)-ATPase activity was obtained. Nor did omeprazole (2 x 10(-4) M) influence HCO3-ATPase. Choline uptake in isolated choroid plexus was significantly reduced by 86% in the presence of acid-pretreated omeprazole 2 x 10(-3) M, but was not affected by 2 x 10(-5) M omeprazole (intact or acid-pretreated). Thus, the mechanism for the marked inhibitory influence of omeprazole on CSF production is not yet evident. In doses causing even a 50% reduction of CSF production, no side effects were observed in contrast to Na(+)-K(+)-ATPase inhibitors such as ouabain.

Nilsson, Christer (författare)
Owman, ChristerLund University,Lunds universitet,Drug Target Discovery,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)mphy-cow (författare)
Winbladh, Birger (författare)
Drug Target DiscoveryForskargrupper vid Lunds universitet (creator_code:org_t)

Av författaren/redakt...: Lindvall-Axelsso ...; Nilsson, Christe ...; Owman, Christer; Winbladh, Birger

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Neurologi

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