EVIDENCE AGAINST CANNABINOID RECEPTOR INVOLVEMENT IN INTRAOCULAR-PRESSURE EFFECTS OF CANNABINOIDS IN RABBITS

Cannabinoid receptor involvement in the intraocular-pressure (IOP)-low ering effect of the cannabinoids has not been determined. These recept ors bind four structural classes of agonists: the classical and the no nclassical cannabinoids, the aminoalkylindoles and the arachidonyletha nolamides (the endogenous ligands). We examined the IOP effect in norm otensive rabbits after systemic administration of an aminoalkylindole, WIN-55,212-2, and of (R)-(+)-methanandamide, a hydrolysis-resistant e ndogenous 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 vehicl e alone. These studies suggest that the IOP-lowering effects of cannab inoids are not mediated by a cannabinoid receptor in rabbits.