OXYMETAZOLINE - POTENTIAL MECHANISMS OF INHIBITORY EFFECTS ON AQUEOUS-HUMOR DYNAMICS

Oxymetazoline, an alpha(2) agonist, was active in lowering intraocular pressure in normal and sympathetically denervated rabbit eyes. Ocular hypotension was accompanied by decreased aqueous humor inflow. Topica l pretreatment with rauwolscine, an alpha(2) antagonist, reduced the o xymetazoline-induced hypotensive effect more in contralateral than in ipsilateral eyes indicating the possible involvement of central alpha( 2) adrenoceptors. Efaroxan, a relatively selective: imidazoline antago nist, and diclofenac, a cyclooxygenase inhibitor, failed to inhibit th e oxymetazoline-induced ocular hypotensive response. Oxymetazoline ind uced mydriasis in treated eyes at all doses. In in vitro studies, oxym etazoline inhibited isoproterenol-stimulated cAMP production in rabbit iris-ciliary bodies and cultured rabbit nonpigmented ciliary epitheli al cells. The inhibition of cAMP accumulation induced by oxymetazoline was antagonized by rauwolscine or by BRL-44408, a relatively selectiv e alpha(2A)-adrenoceptor antagonist. These data indicate that oxymetaz oline lowered intraocular pressure by activating alpha(2A) receptors ( ciliary epithelium) and that the ocular hypotensive effect was not tot ally dependent on intact sympathetic nerves. Results suggest that mech anisms involving centrally mediated effects of oxymetazoline are proba ble and this possibility is currently under investigation.