Inhibition of Cerebrospinal Fluid Formation by a Carbonic Anhydrase Inhibitor,2-Acetylamino-1,3,4-Thiadiazole-5-Sulfonamide (Diamox). ∗

Abstract

Summary

Intravenous 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 HCO_3^- 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 the choroid plexus but throughout the CNS parenchymal vasculature. The interstitial fluid thus formed flows through the pial surface of the CNS into the subarachnoid space and returns to the blood through the arachnoid villi. By decreasing the rate of formation of H⁺ and HCO_3^- within the blood-brain barrier, Diamox diminishes the rate of formation of CNS interstitial fluid and cerebrospinal fluid.