Inhibition of cerebrospinal fluid formation by a carbonic anhydrase inhibitor, 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide (diamox).

Abstract

SummaryIntravenous administration of a carbonic anhydrase inhibitor, 2-acetylamino-1,3, 4-thiadiazole-5-sulfonamide sodium (Diamox), to anesthetized cats and rabbits caused a sustained 3- to 15-fold decrease in rate of cerebrospinal fluid formation resulting in a marked reduction in intracranial pressure. This phenomenon cannot be ascribed to changes in plasma CO2 concentration since prolonged alterations in alveolar CO2 had no effect on the steady state rate of CSF production either before or after Diamox. It is hypothesized that normally the carbonic anhydrase of the central nervous system (CNS) accelerates the formation within the blood-brain barrier of H+ and HCO3- from CNS CO2. These ions are exchanged for plasma anions and cations, largely Na+ and Cl-, which thus enter the interstitial fluid of the CNS. By virtue of the relative impermeability of the blood-brain barrier to electrolytes, water enters from the plasma to maintain osmotic equilibrium. This mechanism is considered to exist not only in th...