HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.
AuthorsFrancesca Fabrizi, Francesco Mincione, Teresa Somma, Gabriele Scozzafava, Fernando Galassi, Emanuela Masini, Francesco Impagnatiello, Claudiu T Supuran
JournalJournal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 27 Issue 1 Pg. 138-47 (Feb 2012) ISSN: 1475-6374 [Electronic] England
PMID21815773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Acrylic Resins
  • Enzyme Inhibitors
  • NCX250
  • Nitrates
  • Sulfonamides
  • Thiophenes
  • carbomer
  • Nitric Oxide
  • dorzolamide
  • Carbonic Anhydrases
  • Isosorbide Dinitrate
  • isosorbide-5-mononitrate
Topics
  • Acrylic Resins
  • Animals
  • Carbonic Anhydrases (metabolism)
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors (chemistry, pharmacology)
  • Glaucoma (chemically induced, drug therapy)
  • Isosorbide Dinitrate (analogs & derivatives, chemistry, pharmacology)
  • Male
  • Molecular Structure
  • Nitrates (chemistry, pharmacology)
  • Nitric Oxide (metabolism)
  • Rabbits
  • Sulfonamides (chemistry, pharmacology)
  • Thiophenes (chemistry, pharmacology)
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: