Therapeutic and systemic side effects of ocular beta-adrenergic antagonists in anesthetized dogs

Beta adrenergic antagonists, while useful in the treatment of glaucoma, can be absorbed transocularly causing a variety of systemic side effects. An adequate animal model which simultaneously indicates the intraocular pressure lowering effects as well as the systemic effects of ocularly applied beta-adrenergic antagonists would be highly useful. The pentobarbital anesthetized dog, instrumented to record blood pressure (BP) and heart rate (HR) and in which intraocular pressure (IOP) was measured with a pneumatonometer, was investigated. Isoproterenol iv dose-response curves were run and IOP measured before and hourly for 3 hr following ocular application of 50 microliters 0.5% RS-52367 (a Syntex beta-adrenergic antagonist), or dH2O control. Timolol and RS-52367 produced similar decreases in IOP. However, timolol decreased basal BP and HR, markedly inhibited isoproterenol-induced BP and HR responses, and also decreased contralateral IOP. Systemic effects of RS-52367 were far more mild. Since both the IOP lowering and systemic beta-adrenergic antagonist properties of timolol were elicited, the anesthetized dog appears to be an excellent animal model for examining the effects of beta-adrenergic antagonists applied topically to the eye.