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FY Chien, R-FF Wang, TW Mittag, SM Podos; Effect of WIN55212-2 on Aqueous Humor Dynamics in Monkeys . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4067.
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Purpose: WIN55212-2, a cannabinoid agonist, reduces intraocular pressure (IOP) in rabbits, normal (N) and glaucomatous monkeys, and in glaucoma patients. Cannabinoids have been shown to interact with CB1 receptors in primary cells from both the ciliary processes and the trabecular meshwork. The purpose of this study is to determine the mechanism by which WIN55212-2 reduces IOP in normotensive monkey eyes when applied topically. Methods: Tonographic outflow facility (C) was measured before and 3 hours after unilateral application of 50µl of 0.5% WIN55212-2 in 6 N monkeys. Baseline aqueous humor flow rates (F) were measured hourly for 4 hours beginning at 9:30 a.m. The following day, 50µl of 0.5% WIN55212-2 was applied to one eye of each monkey of the 6 N monkeys. The flow rates were measured at the same times as on the baseline day beginning 1 hour after drug administration. Results: Three hours after WIN55212-2 administration, C was unchanged (p≷0.3) [0.65 .075 µl/min/mmHg (mean SEM)) (treatment) vs. 0.58 .034 µl/min/mmHg (baseline) or 0.61 .039 µl/min/mmHg (contralateral)]. Intraocular pressure measured tonographically in treated eyes was reduced (p<0.02) by 11% when compared with either baseline values or contralateral control eyes. Aqueous humor flow rates were significantly (p<0.05) reduced by 18% [1.60 0.14 µl/min (treatment) vs. 1.96 0.17 µl/min (contralateral)]. Conclusion: WIN55212-2 reduces IOP by reducing aqueous humor flow.
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