title: Effect of the CB1 receptor antagonist, SR141716A, on cannabinoid-induced ocular hypotension in normotensive rabbits.
abstract: The present study attempts to indirectly determine if a neuronal cannabinoid (CB1) receptor mediates the intraocular pressure (IOP) reduction effects of arachidonoyl ethanolamide (AEA), its R-alpha-isopropyl analog, and the non-classical cannabinoid, CP-55,940. A series of these cannabinoids were dissolved in an aqueous 10-20% 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) solution (containing 3% polyvinyl alcohol) and administered (25-62.5 microg) unilaterally to normotensive rabbit eyes. This was repeated on animals pre-treated with a subcutaneous injection (2.5 mg/kg) of the highly specific CB1 receptor antagonist, SR 141716A, dissolved in an aqueous 42% 2-HP-beta-CD solution. AEA, its R-alpha-isopropyl analog, and CP-55,940 reduced IOP upon topical application to a greater degree than was detected in the untreated eye. This reduction was eliminated for the latter two compounds by subcutaneous (s.c.) pretreatment of the rabbits with the CB1 receptor antagonist, but the IOP properties of AEA remained unchanged. SR 141716A administered alone (s.c.), elevated the IOP of both eyes. A CB1 receptor seems involved in the IOP reduction induced by either R-alpha-isopropyl anandamide or CP-55,940. However, AEA apparently functions through a different mechanism.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, Finland.
authors.forename: D W
authors.initials: DW
authors.lastname: Pate
authors.forename: K
authors.initials: K
authors.lastname: Järvinen
authors.forename: A
authors.initials: A
authors.lastname: Urtti
authors.forename: V
authors.initials: V
authors.lastname: Mahadevan
authors.forename: T
authors.initials: T
authors.lastname: Järvinen
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology*; D063388:Endocannabinoids; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D015814:Ocular Hypotension / Q000139:chemically induced*; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology*; D011817:Rabbits; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D000077285:Rimonabant
chemical_list: D001095:Arachidonic Acids; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant; C078814:anandamide