APRACLONIDINE AND BRIMONIDINE EFFECTS ON ANTERIOR OCULAR AND CARDIOVASCULAR PHYSIOLOGY IN NORMAL AND SYMPATHECTOMIZED MONKEYS

Apraclonidine and brimonidine administered topically to one eye of ket amine-anesthetized normal cynomolgus monkeys each produced a dose-rela ted bilateral reduction in intraocular pressure which was not dependen t on intact sympathetic innervation. Brimonidine was more potent and e fficacious (10-12 mmHg maximum intraocular pressure reduction 2 hr aft er 200 mu g) but produced a shorter-lasting effect than apraclonidine (4 mmHg maximum intraocular pressure reduction 1-6 hr after 600-1000 m u g). Apraclonidine had little effect on pupil diameter, but brimonidi ne produced a dose-related bilateral miosis which was dependent on int act sympathetic innervation. Neither drug significantly affected refra ctive error. Topical brimonidine, but not apraclonidine, produced a do se-dependent reduction in mean arterial blood pressure, while both dru gs lowered heart rate. A dose-dependent bilateral reduction in aqueous humor flow rate calculated over a 6-hr period following drug administ ration was produced by both topical apraclonidine (maximum 30-35% redu ction with 600 mu g) and brimonidine (maximum 30-45% reduction with 50 -250 mu g), which was not dependent on intact sympathetic innervation. Maintenance of blood pressure by intravenous infusion of angiotensin II had no effect on the aqueous humor flow suppression produced by 100 mu g of topical brimonidine, but pentobarbital anesthesia abolished i t. Intracameral injection of 10 mu g brimonidine in rhesus monkeys pro duced an ipsilateral similar to 15 % reduction in aqueous humor now ca lculated for the 1-3 hr post-injection period. The cardiovascular and contralateral ocular effects observed with both drugs are presumably r elated to the monkeys' small body weight, and the magnitude of IOP red uction for a given degree of now suppression would be greater in hyper tensive than in normotensive eyes. Caution must therefore be exercised in extrapolating from our data in ocular normotensive monkeys to the glaucomatous human.