Dorzolomide HCl is a potent and water-soluble inhibitor of human carbonic anhydrase II and IV with Ki of 1.9 nM and 31 nM respectively and used as anti-glaucoma agent.
Carbonic anhydrase (CA) II, a physiologically predominant isoform in CA enzymes, is found in red blood cells and many other tissues and plays major roles in pH regulation of body, protection of electrolyte balance, transportation of water and some metabolic pathways[3]. Dorzolamide hydrochloride, approved in patients with ocular hypertension or open-angle glaucoma, is a water-soluble, potent inhibitor of human CA II and CA IV in vitro, the respective IC50 values being 0.18 nM and 6.9 nM. In contrast, it was found to be a much weaker inhibitor of human CA I (IC50 value of 600 nM). In vivo, the topical administration of one 50 microliters drop of 0.5%, 1% and 2% solutions of dorzolamide maximally lowered the intraocular pressure (IOP) of glaucomatous monkeys by 22%, 30% and 37%, respectively. Good ocular hypotensive activity was also observed in ocular normotensive and hypertensive rabbits[4]. Moreover, dorzolamide (3, 10, or 30 mg/kg/day, ip) synergized the antitumor activity of mitomycin C in EAC (Ehrlich's ascites carcinoma) solid tumor models[5].
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