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Fred Y. Chien, BA; Rong-Fang Wang, MD; Thomas W. Mittag, PhD; Steven M. Podos, MD

Arch Ophthalmol. 2003;121:87-90.

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 CB₁ 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 CB₁ receptor, a new class of antiglaucoma agents that is different from currently used clinical drugs, may have clinical potential.

From the Department of Ophthalmology, Mount Sinai School of Medicine, New York University, New York. The authors have no commercial or financial interest in the drug evaluated in this article. Dr Podos is a consultant to Alcon Laboratories, Inc, Ft Worth, Tex.

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