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A.B. Kharlamb, A.H. Krauss, J. Chen, D.F. Woodward, A.L. Nieves, T. Dinh, R.M. Burk, M. Holoboski, M. Posner, S.F. E. Nilsson; PROSTANOID EP4 RECEPTOR STIMULATION PRODUCES PROFOUND OCULAR HYPOTENSION THAT INVOLVES PRESSURE DEPENDENT OUTFLOW . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1035.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the ocular hypotensive effects of the selective EP4 receptor agonist ONO–123A and its effects on aqueous humor dynamics. Methods: Intraocular pressure (IOP) was measured in laser–induced ocular hypertensive monkeys and ocular normotensive beagle dogs. Ocular surface hyperemia was visually assessed in dogs and graded mild, moderate or severe. Pressure–dependent aqueous humor outflow was determined by the two–level perfusion method. Results: ONO–AEI–329 and an esterified derivative thereof produced a profound decrease in monkey IOP. Single doses in the 0.01 – 0.1% range reduced IOP to the level of the normotensive, vehicle–treated contralateral eye. Such reductions were in the vicinity of 50%. A similar, profound decrease in IOP was found in dogs, where ocular hypotension was accompanied by moderately severe ocular surface redness. No miosis was detected in either species. In monkeys a single topical 0.01 % dose increased outflow facility by 43%. Conclusions:EP4 receptor agonists offer novel anti–glaucoma drugs that directly enhance pressure–dependent outflow. The ocular hypotensive activity is marked and appears to normalize elevated IOP, similar to EP–2 receptor agonists. EP2 and EP4 receptors appear to represent promising targets for the design of future anti–glaucoma drugs.
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