title: Topical application of a nitric oxide synthase inhibitor reduces intraocular pressure in rabbits with experimental glaucoma.
abstract: The role of nitric oxide (NO) in neuronal degeneration of glaucoma is well established, and drugs to inhibit NO production have been introduced in preclinical studies. The present experiments were made to investigate the pharmacological efficacy of a topical formulation of the nonselective nitric oxide synthase (NOS) inhibitor, nitro-L-arginine methyl ester (L-NAME), in an experimental model of glaucoma in rabbits. L-NAME was dissolved in an isotonic, mucoadhesive, viscosized, buffered solution in concentrations of 0.1%, 0.5%, or 1% (w/v). Ocular hypertension (of at least 15 mmHg compared to basal values) was induced by intra-ocular injection of alpha-chymotrypsin. The instillation of L-NAME topical formulations lowered the IOP of hypertensive rabbits in a dose-related manner, with a maximum drop of 12.0 mmHg 60 minutes after administration of the highest concentration. The area under the curve (AUC) of the DeltaIOP (mmHg) versus time (minutes) was 1050.3 +/- 141.7 and 15.1 +/- 2.5 for the 1% L-NAME-treated group and vehicle-treated group, respectively. No change was found in IOP or pupil diameter after instillation of L-NAME eye drops in normotensive rabbits. This study provides the first evidence that topical L-NAME significantly reduces the IOP in a model of ocular hypertension.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Ocular Pharmacology Centre, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Giuffrida
authors.forename: Claudio
authors.initials: C
authors.lastname: Bucolo
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000867:Anterior Chamber; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002918:Chymotrypsin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005901:Glaucoma / Q000139:chemically induced / Q000188:drug therapy*; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000737:chemistry; D011817:Rabbits; D012997:Solvents
chemical_list: D004791:Enzyme Inhibitors; D009883:Ophthalmic Solutions; D012997:Solvents; D019001:Nitric Oxide Synthase; D002918:Chymotrypsin; D019331:NG-Nitroarginine Methyl Ester