Oxymetazoline: Potential Mechanisms of Inhibitory Effects on Aqueous Humor Dynamics

Abstract

Oxymetazoline, an α₂ agonist, was active in lowering intraocular pressure in normal and sympathetically denervated rabbit eyes. Ocular hypotension was accompanied by decreased aqueous humor inflow. Topical pretreatment with rauwolscine, an α₂ antagonist, reduced the oxymetazoline-induced hypotensive effect more in contralateral than in ipsilateral eyes indicating the possible involvement of central α₂ adrenoceptors. Efaroxan, a relatively selective imidazoline antagonist, and diclofenac, a cyclooxygenase inhibitor, failed to inhibit the oxymetazoline-induced ocular hypotensive response. Oxymetazoline induced mydriasis in treated eyes at all doses. In in vitro studies, oxymetazoline inhibited isoproterenol-stimulated cAMP production in rabbit iris-ciliary bodies and cultured rabbit nonpigmented ciliary epithelial cells. The inhibition of cAMP accumulation induced by oxymetazoline was antagonized by rauwolscine or by BRL-44408, a relatively selective α_2A-adrenoceptor antagonist. These data indicate that oxymetazoline lowered intraocular pressure by activating α_2A receptors (ciliary epithelium) and that the ocular hypotensive effect was not totally dependent on intact sympathetic nerves. Results suggest that mechanisms involving centrally mediated effects of oxymetazoline are probable and this possibility is currently under investigation.

Kappa Opioid Agonist-Induced Changes in IOP: Correlation with3H-NE Release and cAMP Accumulation

“…Established ocular hypotensive drugs such as a2 agonists, that depress cAMP formation in ocular tissues, can lower IOP (Chu, Ogidigben and Potter, 1996). It is assumed that kappa agonists, like the aforementioned drugs, could possibly lower IOP by suppressing cAMP formation as well.…”

Naphazoline-induced Suppression of Aqueous Humor Pressure and Flow: Involvement of Central and Peripheral α2/I1Receptors

“…It has been demonstrated previously that the sympathetic tone, cAMP levels and IOP are higher in dark-adapted than in light adapted rabbits (Rowland et al, 1981;Chu, Ogidigben and Potter, 1996), enabling a larger range of response during drug-induced lowering of IOP. Naphazoline (7 .…”

Ocular Hypotension Induced by Electroacupuncture

“…This laboratory has shown that the IOP lowering effect of several drugs that inhibit sympathoadrenal activity is associated with reduction of aqueous humor flow rate (6,7). In this laboratory, aqueous humor flow rates are measured in rabbit eyes using fluorescein dilution as quantified by a Fluorotron Master (Ocumetrics, Palo Alto, CA).…”