Effects and interactions of epinephrine, norepinephrine, timolol, and betaxolol on outflow facility in the cynomolgus monkey.

Total outflow facility was determined in cynomolgus monkeys by two-level constant pressure perfusion. Topical epinephrine increased facility by 30% to 35% three to four hours after dosing, whether given as a single 600-micrograms dose or as twice daily 600-micrograms doses for three days. A single 5.5-micrograms intracameral dose of epinephrine or norepinephrine increased facility by 65% to 70% three to four hours after dosing. A single 180-micrograms topical dose of timolol or betaxolol had no effect on facility three to four hours later. Timolol pretreatment prevented the facility-increasing effect of both topical epinephrine and intracameral norepinephrine, but betaxolol pretreatment prevented neither. These findings indicate that no cumulative facility-increasing effect of epinephrine, beyond the acute (three hour) facility-increasing effect, develops within three days; there may be a facility-decreasing effect of large topical epinephrine doses on the vascular structures external to the trabecular meshwork; there is no, or only subthreshold, facility-affecting ambient beta-adrenergic tone in the meshwork; and the facility-increasing effect of both epinephrine and norepinephrine is mediated by beta 2-adrenergic receptors in the trabecular endothelium.