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AH Krauss, J Chen, A Kharlamb, RM Burk, M Holoboski, M Posner, DW Gil, JA Burke, DF Woodward; A Selective Prostanoid EP2 Receptor Agonist (Butaprost) Normalizes Glaucomatous Monkey Intraocular Pressure . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4107.
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Purpose: Ocular hypertension is a significant risk factor for glaucoma and should be preferably reduced to normal levels. We have compared the activity of different pharmacological classes of ocular hypotensive agents to determine the most effective and which may normalize elevated intraocular pressure. Methods: Intraocular pressure was measured by pneumatonometry in monkeys rendered unilaterally ocular hypertensive by circumferential laser treatment. Pharmacological studies involved radioligand binding and functional studies at recombinant receptors and natural receptors associated with cells and isolated tissues. Results: Butaprost (EP2 agonist) was the only entity that reduced intraocular pressure to that of the contralateral, normotensive eye. This translated into a decrease of ≷ 40%. Differences in the IOP between the butaprost-treated ocular hypertensive eyes and the untreated, control eyes were 11.7 mm Hg immediately before dosing and -0.3 mm Hg at 6 hr post-dosing. A comparison of similar data for other drugs indicated intraocular pressure was not normalized and remained elevated relative to the ocular normotensive control eye. For example, the pretreatment and post-treatment differences between ocular hypertensive eyes and ocular normotensive eyes for PGF2α 1-isopropyl ester (0.01%) were 12.0 and 5.7 mm Hg, respectively. Values for Timolol (0.5%) were 18.9 and 6.8 mm Hg, respectively. Conclusion: The Butaprost results suggest that EP2 agonists are highly efficacious ocular hypotensive agents with the ability to «normalize» elevated intraocular pressure.
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