Carbon Dorzolamide hydrochloride

These constants are similar to those reported for the structurally similar carbonic anhydrase inhibitor, dorzolamide hydrochloride, (6.4 and 8.2,... 

Orally administered carbonic anhydrase inhibitors lower the intraocular pressure of glaucoma patients, however they induce a number of intolerable side effects associated with extraocular inhibition of the enzyme [5,6]. Thus, much research has been directed towards the search for a topically effective agent. Several compounds have been synthesized since the 1980 s in Merck Sharp Dohme Research Laboratories, and have been found to be topically active in man [7]. Unfortunately, many of these compounds were not very soluble. Attempts to obtain an active carbonic anhydrase inhibitor with good solubility resulted in the synthesis of Dorzolamide hydrochloride [8,9], which was first made available for pharmacological evaluation in 1987. Like other carbonic anhydrase inhibitors sulfonamides (such as acetazolamide, ethoxzolaniide, and methazolamide) dorzolamide is an inhibitor of human carbonic anhydrase isoenzymes I, II, and IV. In contrast to the other sulfonamides, dorzolamide is a potent inhibitor of isoenzymes II and IV, and a weak inhibitor of isoenzyme I [ 10]. Isoenzyme II is thought to play a major role in aqueous humor secretion. 

Crude dorzolamide hydrochloride is purified by dissolution in water with heating, and treatment with activated carbon. The final crystallization step provides dorzolamide hydrochloride in the desired form. 

The carbon-13 nuclear magnetic resonance spectrum of a 4.7% (w/v) solution of dorzolamide hydrochloride was obtained in deuterated dimethyl sulfoxide, and is shown in Figure 9. The spectrum was recorded using a Brucker model AM-400 NMR spectrometer. The band assignments were referenced relative to dimethyl sulfoxide-ds (39.5 ppm), and the carbon atom assignments (using the same numbering system as just described) are collected in Table 5. 

Dorzolamide Hydrochloride is an inhibitor of human carbonic anhydrase II. The inhibition of carbonic anhydrase in the ciliary processes of the eye decreases the secretion of aqueous humor, with a resulting reduction in intraocular pressure. The drug is formulated as an ophthalmic solution, and administered topically as eyedrops. 

Although cataract surgery is a potential precursor to bullous keratopathy, there are many other causes. Fuchs endothelial dystrophy, infection, trauma, retained foreign body, posterior polymorphous dystrophy, chronic uveitis, chronically elevated intraocular pressure (lOP), and vitreous touch are all known causes of bullous keratopathy. Other less common causes of bullous keratopathy include corneal thermal injury secondary to carbon dioxide laser skin resurfacing, air bag trauma, the use of topical dorzolamide hydrochloride in glaucoma patients with endothelial compromise, and use of mitomycin C during trabeculectomy surgery. 

The safety profile and efficacy of 2% dorzolamide hydrochloride (Trusopt) eye-drops have been evaluated. It was as effective as pilocarpine 2% and its ocular hypotensive efficacy was comparable with that of betaxolol 0.5%. The patients reported less interference with quahty of life with dorzolamide than pilocarpine, particularly in regard to limitations in their ability to drive, read, and perform moderate activities. Long-term use was not associated with important electrolyte disturbances or the systemic effects commonly observed with oral carbonic anhydrase inhibitors (1-3). 

In this case the allergic reaction was caused by dorzolamide hydrochloride and not the preservative, benzalkonium chloride, since therapy was uneventfully continued with timolol maleate, which also contains benzalkonium chloride as a preservative. This is the first report of this phenomenon with a carbonic anhydrase inhibitor. 

---