Addition of the effects of norepinephrine and acetazolamide to decrease formation of cerebrospinal fluid.

In a system for ventriculocisternal perfusion of the choroid plexus, the rate of formation of new cerebrospinal fluid was measured by changes in dilution of an impermeant dye in the perfusate. Norepinephrine added to the perfusate decreased formation of cerebrospinal fluid in rats as was previously demonstrated in rabbits. The dose-response relationship for rats was determined. The formation rate was decreased 42% by 10(-3) M norepinephrine. Acetazolamide, 50 mg/kg i.v., caused a decrease of 46%. Given together, these drugs decreased formation 79%, demonstrating essentially full addition between the regulatory mechanisms involved. Addition of equal magnitude occurred when intraventricular nialamide, an inhibitor of monoamine oxidase, and i.v. acetazolamide were given together. This demonstrates addition between acetazolamide and endogenous norepinephrine (or other catecholamines present) in which metabolic breakdown is prevented by the inhibitor. The degree of reduction in cerebrospinal fluid formation seen in these experiments exceeds that reported for numerous other trials of single drugs.