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. Topical pretreatment with rauwolscine, an alpha 2 antagonist, reduced the oxymetazoline-induced hypotensive effect more in contralateral than in ipsilateral eyes indicating the possible involvement of central alpha 2 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 alpha 2A-adrenoceptor antagonist. These data indicate that oxymetazoline lowered intraocular pressure by activating alpha 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.
Chu
T C
TC
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Ga 30310-1495, USA.
Ogidigben
M J
MJ
Potter
D E
DE
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects*; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003714:Denervation; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects; D007498:Iris / Q000378:metabolism; D008029:Lighting; D008297:Male; D010109:Oxymetazoline / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D010109:Oxymetazoline; D000242:Cyclic AMP