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 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.


CONCLUSIONS
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.
Chien
Fred Y
FY
Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Wang
Rong-Fang
RF
Mittag
Thomas W
TW
Podos
Steven M
SM
D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D048588:Benzoxazines; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002186:Cannabinoids / Q000819:agonists; D004195:Disease Models, Animal; D005260:Female; D015590:Fluorophotometry; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects*; D017075:Laser Coagulation; D008252:Macaca fascicularis; D009025:Morpholines / Q000008:administration & dosage*; D009281:Naphthalenes / Q000008:administration & dosage*; D009883:Ophthalmic Solutions; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists*; D014065:Tonometry, Ocular; D014129:Trabecular Meshwork / Q000601:surgery
D048588:Benzoxazines; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D009883:Ophthalmic Solutions; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone