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Carol Toris, Tara Rudebush, Stacey Wenthur, David Woodward; Comprehensive Analysis of Prostanoid Receptor Antagonists Effects on Intraocular Pressure in Ocular Hypertensive Monkeys. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3702. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Most of what is known about prostanoid receptor mediated control of IOP has been learned from studies of prostanoid agonists. Prostanoid antagonist effects have been studied largely from the perspective of confirming the pharmacological identity of prostanoid agonists in producing their effects. This study examines the IOP effects of 8 prostanoid receptor antagonists in monkeys with unilateral laser-induced glaucoma to better understand a possible role of endogenous prostaglandins in the regulation of IOP.
Eight trained conscious monkeys were studied. Baseline IOPs were taken by pneumatonometry of both eyes at 9AM. The study compound was applied topically to the glaucomatous eye at 9:05. IOP measurements were repeated at 10AM, 12PM, 2PM, and 4PM and daily at 9AM for the next three days. After 6 days of washout, another compound was applied. IOPs were repeated as at baseline. Randomized dosing and IOP measurements continued until all compounds were tested. Antagonists dosed at 1% were SC-51322 (EP1), PF-04418948 (EP2), L-826266 (EP3), GW-627368 (EP4), BW-A868C (DP1), AGN-211336 (prostamide), AS- 604872 (FP), RO-3244019 (IP). The vehicle was 1% Polysorbate 80.
When compared with vehicle treatment, significant (p<0.05) findings were higher IOPs with the EP1 and EP2 antagonists at 3 hours, and IP and EP4 antagonists at 7 hours after dosing. The increases were small and transient. No other antagonist changed IOP compared to vehicle.
The implication of these findings is that endogenous prostanoids, predominantly EPs, are involved in decreasing IOP. Apparently exogenously administered prostanoid antagonists interfere only with those receptors under endogenous prostanoid control which are anatomically located such that they maintain an IOP within a healthy range.
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