Can UK-14, 304-18 lower IOP in rabbits by a peripheral mechanism?

Unilateral topical administration of alpha 2 adrenoceptor agonists lowers intraocular pressure (IOP) bilaterally in laboratory animals and man. Investigators have suggested that this decrease in IOP is mediated, in part, by alpha 2 adrenoceptors in the central nervous system (CNS). In the present study, the hypotensive activity of the alpha 2 agonist, UK-14,304-18 (UK), was evaluated following topical and intracameral administration. The unilateral administration of a relatively selective alpha 2 adrenoceptor agonist, UK (50 micrograms), lowered IOP bilaterally when applied topically to the eyes of rabbits. Intracamerally administered UK (0.05-50 ug) lowered IOP unilaterally in a dose-related manner with minimal pupillary and cardiovascular changes. The ocular hypotensive action of UK administered intracamerally was absent in rabbits that had been surgically sympathectomized. While these data demonstrate that UK can lower IOP in the rabbit independent of alpha 2 adrenoceptor stimulation in the CNS and other systemic sites, the expression of this response is dependent upon the presence of intact sympathetic innervation.