title: A new approach to antiglaucoma drugs: carbonic anhydrase inhibitors with or without NO donating moieties. Mechanism of action and preliminary pharmacology.
abstract: The clinically used sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor dorzolamide (DRZ), a new sulfonamide CA inhibitor also incorporating NO-donating moieties, NCX250, and isosorbide mononitrate (ISMN) (an NO-donating compound with no CA inhibitory properties) were investigated for their intraocular pressure (IOP) lowering effects in rabbits with carbomer-induced glaucoma. NCX250 was more effective than DRZ or ISMN on lowering IOP, increasing ocular hemodynamics, decreasing the inflammatory processes and ocular apoptosis in this animal model of glaucoma. NO participate to the regulation of IOP in glaucoma, having also antiapoptotic and anti-inflammatory effects. The ophthalmic artery, both systolic and diastolic velocities, were significantly reduced in NCX250-treated eyes in comparison to DRZ treated ones, suggesting thus a beneficial effect of NCX250 on the blood supply to the optic nerve. Combining CA inhibition with NO-donating moieties in the same compound offers an excellent approach for the management of glaucoma.
authors.affiliation: Università degli Studi di Firenze, Department of Preclinical and Clinical Pharmacology, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fabrizi
authors.forename: Francesco
authors.initials: F
authors.lastname: Mincione
authors.forename: Teresa
authors.initials: T
authors.lastname: Somma
authors.forename: Gabriele
authors.initials: G
authors.lastname: Scozzafava
authors.forename: Fernando
authors.initials: F
authors.lastname: Galassi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Masini
authors.forename: Francesco
authors.initials: F
authors.lastname: Impagnatiello
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000180:Acrylic Resins; D000818:Animals; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005901:Glaucoma / Q000139:chemically induced / Q000188:drug therapy*; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009566:Nitrates / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000180:Acrylic Resins; D004791:Enzyme Inhibitors; C572403:NCX250; D009566:Nitrates; D013449:Sulfonamides; D013876:Thiophenes; C479038:carbomer; D009569:Nitric Oxide; C062765:dorzolamide; D002256:Carbonic Anhydrases; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate