Effect of WIN 55212-2, a cannabinoid receptor agonist, on aqueous humor dynamics in monkeys

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.