COMPARISON OF EFFECTS OF TIMOLOL AND OTHER ADRENERGIC AGENTS ON INTRAOCULAR-PRESSURE IN RABBIT

Abstract

The effect of timolol, propranolol, epinephrine and isoproterenol on intraocular pressure (IOP) (measured by tonometry) were compared after topical administration in conscious rabbits. Epinephrine and isoproterenol decreased IOP in normotensive rabbits, whereas propranolol had no effect. Timolol produced only a slight and inconsistent lowering of IOP in normotensive rabbits. All 4 agents reduced IOP elevated by an oral water load; the adrenergic agonists were substantially more active than the 2 .beta.-adrenergic blocking agents. In .alpha.-chymotrypsin-induced ocular hypertension, epinephrine, isoproterenol and timolol were essentially equally effective, whereas propranolol exhibited only weak activity. In this latter model, timolol did not lose its effectiveness after multiple instillations (3/day) over an 8 day period. The concentration of timolol in the aqueous humor after topical application of effective hypotensive doses was relatively high compared to that in plasma. Topical doses of timolol required to lower IOP were considerably greater than those needed to reduce or block the ocular hypotensive activity of isoproterenol. The mode of action and therapeutic implications of .beta.-adrenergic blocking agents in glaucoma were discussed.