Administration iv of 50 mg X kg-1 acetazolamide (A) and 3 mg X kg-1 timolol (T) causes the formation of cerebrospinal fluid (f-CSF) to be reduced to 43.7% of the control rate compared with a reduction to 82.5% of control by T alone and to 52.6% of control by A alone. The effect of combined drugs is the same when A is combined with T initially, when A is added to T after studying T alone, or when T is added to A after studying A alone. In contrast, in rats f-CSF is not influenced by T, either alone or when in combination with A. The rate in rats is reduced to 55% of control by treatments with A or A and T. Decrease in formation of cerebrospinal fluid by A occurs through inhibition of carbonic anhydrase, but the means whereby T (a known blocker of beta-adrenergic receptors) causes a reduction in f-CSF is not established; it is known that it does not inhibit carbonic anhydrase. Control of f-CSF by the sympathetic nervous system is discussed.

No abstract

No abstract

The influence of timolol upon cerebrospinal fluid formation rate has been examined in rats by the measurement of 22Na+ entry into this fluid after 10, 100, or 1000 micrograms x kg-1 i.v. and in cats by the dye-dilution measurement of new fluid formation after 30, or 3000 microgram x kg-1 i.v., or 250 micrograms x mL-1 in ventricular perfusate. In rats no change from control rates occurred. In the cats there appeared to be no effect of intraventricular timolol; however, a significant decrease of approximately 25% in the mean flow rate was seen after 40 min when drug was given i.v. at either dose level. A time study showed that no further decrease occurred within 5 h and that the observed decrease continued for at least 3 h. These findings are of interest in view of the ability of topical, intraocular, and i.v. timolol to reduce aqueous humor formation rate.