Abstract

The ability of acetazolamide and furosemide to inhibit cerebrospinal fluid (CSF) flow and choroid plexus carbonic anhydrase was measured in adult New Zealand White rabbits of either sex. CSF formation rates were measured by the inulin-dilution technique and carbonic anhydrase activity by the changing-pH method. The maximal reduction in CSF flow with either drug was between 50 and 60%. Acetazolamide did not decrease CSF flow rate until over 99.5% of choroid plexus carbonic anhydrase was inhibited. In contrast, furosemide caused a significant decrease in CSF flow with less than 98% inhibition of choroid plexus carbonic anhydrase. In vitro studies showed that acetazolamide is about 100 times as potent as furosemide in the inhibition of carbonic anhydrase of the choroid plexus. Based on the assumption that the decrease in CSF flow with acetazolamide is due solely to carbonic anhydrase inhibition, then furosemide must be acting, at least partially, by a mechanism other than the inhibition of choroid plexus carbonic anhydrase. If acetazolamide and furosemide decrease flow by different mechanisms, the effects of the two drugs may be additive with respect to inhibition of CSF flow and it may be possible to reduce CSF flow more than the approximately 50% that can be accomplished with the individual therapeutic agents presently in use.