The effect of cyclooxygenase inhibition on the ocular hypotensive action of topical carbonic anhydrase inhibitors in rabbits.
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.
Sugrue
M F
MF
Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania.
O'Neill-Davis
L
L
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002257:Carbonic Anhydrase Inhibitors; D016861:Cyclooxygenase Inhibitors; D004837:Epinephrine