Aqueous humor dynamics in monkeys in response to the kappa opioid agonist bremazocine.

PURPOSE To determine the effects of the kappa opioid agonist, bremazocine (BRE), on intraocular pressure (IOP) and aqueous humor dynamics in normotensive cynomolgus monkeys. METHODS IOP, pupil diameter, refraction, aqueous humor flow, and mean arterial pressure (MAP) were measured following unilateral topical application of 1 to 100 microg BRE. IOP and MAP responses to 100 microg BRE were repeated during intravenous infusion of angiotensin II (ATII). IOP and MAP responses to BRE were also measured following pretreatment with the opioid receptor antagonists norbinaltorphimine (nor-BNI) or naloxone. Outflow facility was measured following unilateral intracameral exchange with 0.01 to 100 microg/mL BRE. IOP, aqueous humor flow, pupil, and MAP were measured after unilateral intracameral bolus injection of 1 microg of BRE. RESULTS Unilateral topical BRE caused a dose-related reduction in IOP and aqueous humor flow in both eyes and in MAP. Pupil miosis occurred at the 100-microg dose. There was no effect on refraction. IOP and MAP decreases after 100 microg of BRE were eliminated by ATII infusion. Differential IOP effects after 10-microg topical BRE doses were not eliminated by nor-BNI or naloxone. Unilateral intracameral bolus injection of BRE decreased IOP in both eyes but had no effect on MAP or aqueous humor flow. Outflow facility was unchanged after intracameral exchange with BRE. CONCLUSIONS The IOP response to high doses of BRE in monkeys can be attributed to peripheral or central effects on MAP. The IOP-lowering response to topical BRE is due to aqueous humor flow suppression via non-opioid receptor stimulation. Some components of the IOP response are mediated by unknown mechanisms.