Effect of 0.04% AR-13324, a ROCK, and Norepinephrine Transporter Inhibitor, on Aqueous Humor Dynamics in Normotensive Monkey Eyes. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Wang, Rong-Fang; Williamson, Jennifer E.; Kopczynski, Casey; Serle, Janet B.
• Is Part Of: Journal of glaucoma. Volume 24:Issue 1(2015:Jan.)
• Publication Date: 2015-01
• Subjects: Glaucoma -- Periodicals; 617.741005
• DOI: 10.1097/IJG.0b013e3182952213
• Languages: English
• ISSNs: 1057-0829

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Purpose:</title> <p>To determine the mechanism by which topically applied AR-13324, a rho kinase inhibitor, and an inhibitor of the norepinephrine transporter, reduces intraocular pressure (IOP) in normotensive monkey eyes.</p> </sec> <sec> <title>Methods:</title> <p>Seven normotensive monkeys were used. Tonographic outflow facility (<italic>C</italic>) was measured before drug administration and repeated 6 hours after administration of 50 µL (25 µL×2) of 0.04% AR-13324 to 1 eye and an equal volume of vehicle to the contralateral control eye. Baseline aqueous humor flow rates (<italic>F</italic>) were measured hourly for 6 hours beginning at 10:00 AM on day 1. On day 2, 50 µL (25 µL×2) of 0.04% AR-13324 was applied to 1 eye of each animal and vehicle to the fellow eye at 8:00 AM. Aqueous humor flow rates were measured at the same times as on the baseline day beginning 2 hours after dosing.</p> </sec> <sec> <title>Results:</title> <p>Six hours after a single dose of 0.04% AR-13324 to 7 normal monkey eyes, <italic>C</italic> was increased (<italic>P</italic><0.05) by 53% in drug-treated eyes compared with either contralateral vehicle-treated control eyes or baseline measurements. The IOP measured by pneumatonometer in treated eyes was reduced (<italic>P</italic><0.005) by 25% when compared with baseline measurements and by 24% when compared with contralateral vehicle-treated eyes. For 6 hours after a single dose of 0.04% AR-13324, <italic>F</italic> was reduced (<italic>P</italic><0.05) by 20% and 23% when compared with contralateral vehicle-treated eyes and baseline values, respectively.</p> </sec> <sec> <title>Conclusions:</title> <p>AR-13324 reduces IOP in normotensive monkey eyes. A dual mechanism of action, increase in tonographic outflow facility, and decrease of aqueous humor flow rates, accounts for the IOP reduction in normotensive monkey eyes.</p> </sec> </abstract>