title: The effect of cyclooxygenase inhibition on the ocular hypotensive action of topical carbonic anhydrase inhibitors in rabbits.
abstract: Experiments were undertaken in normal albino rabbits to determine if cyclooxygenase inhibition by nonsteroidal anti-inflammatory drugs modified the ocular hypotensive activities of topically applied MK-507, MK-927 and L-662,583, three water-soluble carbonic anhydrase inhibitors (CAI). Cyclooxygenase was inhibited either by systemic indomethacin or by topically administered flurbiprofen, and epinephrine was included as a positive control. Both a 1-hr pretreatment with indomethacin (5 mg/kg i.p.) and topically applied 0.03% flurbiprofen antagonized the ocular hypotensive effect of one drop (50 microliters) of 1% epinephrine. Two percent solutions of the three CAIs were instilled three times with 10 min between each drop in order to obtain a meaningful and reproducible reduction in intraocular pressure (IOP). This dosage schedule elicited a peak decline in IOP ranging from 4.6 mm Hg to 6.2 mm Hg which was achieved via a local action within the eye. The ocular hypotensive effects of MK-507, MK-927 and L-662,583 were unaltered either by a 1-hr pretreatment with indomethacin (5 mg/kg i.p.) or by topically administered 0.03% flurbiprofen. These studies indicate that the IOP lowering actions of the three CAIs, unlike that of epinephrine, in rabbits are not mediated by endogenous prostaglandins and/or other prostanoids.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania.
authors.forename: M F
authors.initials: MF
authors.lastname: Sugrue
authors.forename: L
authors.initials: L
authors.lastname: O'Neill-Davis
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D011817:Rabbits
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002257:Carbonic Anhydrase Inhibitors; D016861:Cyclooxygenase Inhibitors; D004837:Epinephrine