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1 General aspects (0)   1.1 Epidemiology (20)   1.2 Population genetics (2)   1.3 Pathogenesis (6)   1.4 Quality of life (12)   1.5 Glaucomas as cause of blindness (5)   1.6 Prevention and screening (9) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (16)   2.2 Cornea (12)   2.3 Sclera (9)   2.4 Anterior chamber angle (10)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (10)     2.5.2 Schlemms canal (1)     2.5.3 Scleral outlet channels (0)   2.6 Aqueous humor dynamics (0)     2.6.1 Production (0)     2.6.2 Outflow (0)       2.6.2.1 Trabecular meshwork (3)       2.6.2.2 Uveoscleral (3)     2.6.3 Compostion (4)   2.7 Episcleral veins and venous pressure (0)   2.8 Iris (7)   2.9 Ciliary body (0)   2.10 Lens (0)   2.11 Vitreous body (0)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (4)   2.13 Retina and retinal nerve fibre layer (23)   2.14 Optic disc (23)   2.15 Optic nerve (12)   2.16 Chiasma and retrochiasmal central nervous system (12)   2.17 Stem cells (5)   2.20 Other (0) 3 Laboratory methods (0)   3.1 Microscopy (1)   3.2 Electron microscopy (0)   3.3 Immunohistochemistry (1)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (6)     3.4.2 Gene studies (28)   3.5 Molecular biology incl. 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Miscellaneous (28)

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Abstract #48525 Published in IGR 14-1

A new approach to antiglaucoma drugs: carbonic anhydrase inhibitors with or without NO donating moieties Mechanism of action and preliminary pharmacology

Fabrizi F; Mincione F; Somma T; Scozzafava G; Galassi F; Masini E; Impagnatiello F; Supuran CT
Journal of Enzyme Inhibition and Medicinal Chemistry 2012; 27: 138-147

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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.

Università degli Studi di Firenze, Department of Preclinical and Clinical Pharmacology, Florence, Italy.

Full article

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Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)

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