Cannabinoid receptor involvement in the intraocular-pressure (IOP)-lowering effect of the cannabinoids has not been determined. These receptors bind four structural classes of agonists: the classical and the nonclassical cannabinoids, the aminoal-kylindoles and the arachidonylethanolamides (the endogenous ligands). We examined the IOP effect in normotensive rabbits after systemic administration of an aminoalkylindole, WIN-55,212-2, and of (R)-(+)-methanandamide, a hydrolysis-resistant endogenous ligand derivative. The decrease in IOP for 6 animals treated with WIN-55,212-2 was marginal and for 6 animals treated with (R)-(+)-methanandamide was negligible compared to animals treated with vehicle alone. These studies suggest that the IOP-lowering effects of cannabinoids are not mediated by a cannabinoid receptor in rabbits.

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