HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

[Pharmacological profiles of the potent carbonic anhydrase inhibitor dorzolamide hydrochloride, a topical antiglaucoma agent].

Abstract
Carbonic anhydrase (CA) plays an important role in the secretion of aqueous humor. The orally administered CA inhibitor acetazolamide lowers the intraocular pressure (IOP) of patients with glaucoma. However, approximately 50% of patients stop treatment with acetazolamide as a consequence of intolerable side effects due to the extraocular inhibition of the enzyme. This prompted attempts to develop a topically active CA inhibitor. Merck Research Laboratories focused on developing a water- and solvent-soluble compound to penetrate the cornea. Dorzolamide hydrochloride is a potent inhibitor of human CA isoenzyme II, with an IC50 value of 0.18 nM in vitro. In contrast, its inhibitory activity against human CA isozyme I is much weaker (IC50 value of 600 nM). Topically administered dorzolamide penetrated the ciliary body, inhibited its CA activity and had a hypotensive effect in rabbits; in contrast, topical administration of acetazolamide or methazolamide did not decrease IOP. In clinical trials, dorzolamide administered 3 times daily was effective in lowering IOP in patients with open-angle glaucoma or ocular hypertension. The hypotensive effect of dorzolamide 0.5% was similar to that of oral CA inhibitors or timolol (0.25%) twice daily. Dorzolamide did not induce the severe systemic adverse events associated with oral CA inhibitors. Dorzolamide was as effective as pilocarpine or dipivefrine as an adjunctive therapy in patients receiving beta-adrenergic antagonists. Dorzolamide also reduced IOP and accelerated retinal arteriovenous passage time in addition to improving visual function in patients with normal-tension glaucoma.
AuthorsM Kobayashi, K Naito
JournalNihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 115 Issue 6 Pg. 323-8 (Jun 2000) ISSN: 0015-5691 [Print] Japan
PMID10948564 (Publication Type: English Abstract, Journal Article, Review)
Chemical References
  • Antihypertensive Agents
  • Carbonic Anhydrase Inhibitors
  • Ophthalmic Solutions
  • Sulfonamides
  • Thiophenes
  • dorzolamide
Topics
  • Animals
  • Antihypertensive Agents (pharmacokinetics, pharmacology, therapeutic use)
  • Carbonic Anhydrase Inhibitors (pharmacokinetics, pharmacology, therapeutic use)
  • Clinical Trials as Topic
  • Eye (metabolism)
  • Glaucoma, Open-Angle (drug therapy)
  • Humans
  • Intraocular Pressure (drug effects)
  • Ocular Hypertension (drug therapy)
  • Ophthalmic Solutions
  • Rabbits
  • Sulfonamides (pharmacokinetics, pharmacology, therapeutic use)
  • Thiophenes (pharmacokinetics, pharmacology, therapeutic use)

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: