title: Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Seven normotensive monkeys were used. Tonographic outflow facility (C) 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 (F) 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.
  
  
  RESULTS
  Six hours after a single dose of 0.04% AR-13324 to 7 normal monkey eyes, C was increased (P<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 (P<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, F was reduced (P<0.05) by 20% and 23% when compared with contralateral vehicle-treated eyes and baseline values, respectively.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY †Aerie Pharmaceuticals Inc., Research Triangle Park, NC.
authors.forename: Rong-Fang
authors.initials: RF
authors.lastname: Wang
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Williamson
authors.forename: Casey
authors.initials: C
authors.lastname: Kopczynski
authors.forename: Janet B
authors.initials: JB
authors.lastname: Serle
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001082:Aqueous Humor / Q000502:physiology*; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D008252:Macaca fascicularis; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D009883:Ophthalmic Solutions; D014065:Tonometry, Ocular; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000959:Antihypertensive Agents; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009883:Ophthalmic Solutions; D054460:rho-Associated Kinases