Apraclonidine and timolol. Combined effects in previously untreated normal subjects

Twenty healthy subjects were tested for the aqueous-suppressing effects of the alpha 2-adrenergic agonist apraclonidine hydrochloride. Apraclonidine caused a 30% reduction of mean (+/- SD) aqueous flow during the daytime from 2.84 +/- 0.61 microL/min, similar to what has been observed for beta-adrenergic antagonists. Apraclonidine, like acetazolamide and unlike timolol maleate, was able to suppress the aqueous flow of sleeping subjects below the spontaneous nocturnal rate of 1.15 +/- 0.40 microL/min to 0.84 +/- 0.28 microL/min, a 27% change. When apraclonidine and timolol were given together in the daytime, no clinically significant or statistically significant additive effect was observed. The range of flows with either drug alone or the combination of the two measured from 2 to 4 PM was 1.41 to 1.78 microL/min. This result contrasts with studies of the effect of apraclonidine on patients who have received long-term beta-blockers where an additive effect is observed. The lack of an additive effect on flow in previously untreated normal subjects suggests that the two drugs act at least in part via a common pathway.