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Effect of WIN 55212-2, a cannabinoid receptor agonist, on aqueous humor dynamics in monkeys
Fred Y Chien1, Rong-Fang Wang, Thomas W Mittag
1Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Objective:
To evaluate the effects of WIN 55212-2, a cannabinoid receptor agonist, on intraocular pressure and aqueous humor dynamics in normal monkeys and monkeys with glaucoma.
Methods:
Intraocular pressure was measured prior to and up to 6 hours after the topical administration of WIN 55212-2 to 1 eye of 5 normal monkeys and to the glaucomatous eye of 8 monkeys with unilateral laser-induced glaucoma. Tonographic outflow facility and fluorophotometric flow rates of aqueous humor were measured in 6 normal monkeys before and after treatment.
Results:
In normal monkeys, a single dose of WIN 55212-2 reduced intraocular pressure for 4, 5, or 6 hours, with a maximum reduction of 1.4 +/- 0.4 (mean +/- SEM) mm Hg, 2.9 +/- 0.4 mm Hg, and 3.4 +/- 0.6 mm Hg following the 0.07%, 0.2%, and 0.5% concentrations, respectively (P =.08). In 8 glaucomatous monkey eyes, the ocular hypotensive effect was maintained for 5 days with twice-daily administration of 0.5% WIN 55212-2. Outflow facility was unchanged (P =.34) and aqueous humor flow was decreased by 18% (P =.04) in the treated eyes compared with vehicle-treated contralateral control eyes in normal monkeys.
Conclusions:
WIN 55212-2, a cannabinoid agonist at the CB(1) receptor, reduces intraocular pressure in both normal and glaucomatous monkey eyes. A decrease of aqueous flow appears to account for the intraocular pressure reduction in normal monkey eyes.
Clinical Relevance:
Cannabinoid agonists at the CB(1) receptor, a new class of antiglaucoma agents that is different from currently used clinical drugs, may have clinical potential.