Modulation of Ocular Hydrodynamics and Iris Function by Bremazocine, a Kappa Opioid Receptor Agonist

Abstract

This study was designed to determine the activity of bremazocine (BRE), a relatively selective kappa opioid receptor agonist, on intraocular pressure (IOP), aqueous humor formation and pupil diameter (PD) in conscious, normal, dark-adapted New Zealand white (NZW) rabbits. IOP was measured in normal and unilaterally sympathectomized rabbits using a calibrated pneumatonometer and the aqueous flow rate was determined by the use of a Fluorotron Master. A masked-design study was conducted in which the rabbits' eyes were treated with BRE topically and unilaterally; the fellow eyes received vehicle. IOP and PD measurements were taken at 0.5hr and 0 time before BRE and 0.5, 1, 2, 3, 4 and 5hr post-treatment. Fluorophotometry recordings were taken at 1hr before and 0.5, 1.5, 2.5 and 3.5hr after topical application of the drug or vehicle. The effect of the relatively selective kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI), on bremazocine-induced changes in IOP, PD and aqueous flow was also determined. BRE (10 and 100μ g 25μ l−1vehicle) produced dose-related, bilateral reductions in IOP, PD and aqueous humor flow. A large increase in IOP (14mmHg) was observed when BRE (100μ g) was applied to sympathectomized eyes. This ocular hypertensive effect was antagonized when the sympathectomized eyes were pretreated with naloxone (200μ g), a non-selective opioid receptor antagonist. BRE (10 and 100μ g) decreased the aqueous humor flow rate bilaterally by approximately 48 and 60%, respectively, at 0.5hr after administration to the ipsilateral eye. Nor-BNI (100μ g) antagonized the effect of BRE (10μ g) on IOP and aqueous flow rates more effectively than on PD. These data indicate that bremazocine causes reductions in IOP by suppressing aqueous flow, but the ocular hypotensive effects are dependent on the presence of intact sympathetic nerves. Antagonism of BRE's effects on aqueous humor dynamics by nor-BNI suggests that the mechanism of IOP and aqueous flow reduction may involve, in part, an action on kappa receptors. Further experiments are necessary to fully define the opioid receptor populations in the ciliary body.