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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor.

Dorzolamide hydrochloride (S,S-5,6-dihydro-4H-4-ethylamino-6-methylthieno [2,3-b]thiopyran-2-sulfonamide-7,7-dioxide HCl; MK-507; L-671,152) is a water-soluble, potent inhibitor of human carbonic anhydrase isoenzymes II and 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 carbonic anhydrase isoenzyme I (IC50 value of 600 nM). 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. Its site of action was within the eye, and the reductions in IOP in both species was achieved via decreased aqueous humor inflow. The duration of action of 2% dorzolamide was shorter than that of 0.5% timolol in glaucomatous monkeys. The IOP lowering activity of timolol in this paradigm was enhanced by the concomitant instillation of dorzolamide. Both acutely and repeatedly administered 2% dorzolamide did not decrease regional ocular blood flow in the rabbit, and the topical instillation of the drug had no adverse effects on the eye of rabbits, dogs and monkeys. Dorzolamide has been approved in a number of countries for use in patients with ocular hypertension or open-angle glaucoma.[1]


  1. The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor. Sugrue, M.F. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. (1996) [Pubmed]
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