Disease relevance of dorzolamide

• METHODS: According to a 4 x 4 Latin squares design for repeated measures, 27 untreated patients and patients with newly diagnosed primary open-angle glaucoma (POAG) were treated with timolol 0.5% at 8 AM and 8 PM; brimonidine 0.2% at 8 AM and 8 PM; dorzolamide 2% at 8 AM, 2 PM, and 8 PM; and latanoprost 0.005% at 8 PM [1].
• Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hypertension [2].
• Because these processes may play a role in diabetic retinopathy, the authors undertook this study to investigate the protective action of dorzolamide, an inhibitor of carbonic anhydrase, on retinal neural cells [3].
• RESULTS: Dorzolamide-treated eyes were not significantly different from placebo-treated eyes in corneal deswelling rate, expressed as the percent recovery per hour (55.7% +/- 13.6% versus 59.6% +/- 14.5%; P > or = 0.10), open eye steady state thickness, swelling induced by hypoxia, and corneal autofluorescence [4].
• Nephrolithiasis with dorzolamide [5].

Psychiatry related information on dorzolamide

• Anorexia, depression and dementia induced by dorzolamide eyedrops (Trusopt) [6].

High impact information on dorzolamide

• Like oral CA inhibitors, topically applied dorzolamide lowers IOP by decreasing the production of aqueous humor [7].
• Dorzolamide is a very potent inhibitor of CA-II and its site of action is local within the eye [7].
• This is in harmony with the inability of dorzolamide at steady-state to saturate CA in the red blood cell and the failure to detect its presence in plasma [7].
• Some clinically used compounds, such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, sulpiride, and indisulam, or the orphan drug benzolamide, showed effective hCA VI inhibitory activity, with inhibition constants of 0.8-79 nM [8].
• PURPOSE: To compare the short-term effects of timolol 0.5%, brimonidine 0.2%, dorzolamide 2%, and latanoprost 0.005% on intraocular pressure (IOP), blood pressure (BP), and diastolic ocular perfusion pressure (DOPP), calculated as the difference between the diastolic blood pressure (DBP) and IOP [1].

Chemical compound and disease context of dorzolamide

• Short-term ocular tolerability of dorzolamide 2% and brinzolamide 1% vs placebo in primary open-angle glaucoma and ocular hypertension subjects [9].
• Results of the study indicate that it is possible to develop a safe (as indicated by corneal toxicity studies) and physiologically active topical niosomal formulation of acetazolamide relative in efficiency to the newer local carbonic anhydrase inhibitor, dorzolamide [10].
• Eligibility criteria: open-angle glaucoma; IOP > or = 21 mm Hg upon the combination of a non-selective beta-blocker with pilocarpine or dorzolamide or both; no previous bulbar surgery; and prior glaucoma therapy lasting at least 2 years [11].
• Furthermore, dorzolamide is a sulfonamide and can cause allergic reactions in those who are hypersensitive to this class of drug [12].
• Following the addition of dorzolamide as adjunctive therapy to timolol maleate there was a significant reduction in IOP (p < 0.05) at all time points in both glaucomas, but mean IOP at 10:00, 14:00, 18:00 and 22:00 hour time points, as well as the peak and range of IOP, remained higher in the exfoliation glaucoma group [13].

Biological context of dorzolamide

• The intraocular pressure was significantly reduced in all groups after dorzolamide [14].
• Clinical pharmacokinetics of dorzolamide [15].
• PURPOSE: To evaluate the concentration and kinetics of dorzolamide in the aqueous humor after its topical application [16].
• CONCLUSIONS: Dorzolamide reduced the damage inflicted on retinal neural cells by agents that induced apoptosis and, therefore, can be considered a neuroprotectant [3].
• Component A, caused by an inward flux of CO(2) and its subsequent hydration by CA-II, was blocked by dorzolamide in a dose-dependent manner with an 50% inhibitory concentration (IC)(50) of 2.4 micro M (95% confidence interval: 0.5 -10.85 microM) [17].

Anatomical context of dorzolamide

• Inhibition of carbonic anhydrase activity in cultured bovine corneal endothelial cells by dorzolamide [17].
• The resistance index was significantly lower in the ophthalmic and central retinal arteries in all groups after dorzolamide [14].
• Because these levels are encountered in the cornea and aqueous humor after topical administration, dorzolamide may compromise corneal hydration control, especially when the functional reserve of corneal endothelium is low [17].
• The minimal velocity of the central retinal vein showed significantly higher values after dorzolamide, whereas the maximal velocity remained unchanged [14].
• These results suggest that CYP2B, CYP2E1, and CYP3A subfamilies are involved in the dorzolamide N-deethylation in rat liver microsomes [18].

Associations of dorzolamide with other chemical compounds

• To prove that the tail (in this case the pyridinecarboxylic moieties) conferring water solubility to a sulfonamide CA inhibitor is more important than the ring to which the sulfonamido group is grafted, we also prepared dorzolamide derivatives incorporating such moieties [19].
• RESULTS: Intraocular pressure reduction was greater on average in the combination group than in the dorzolamide and timolol groups [20].
• OBJECTIVE: To determine whether dosages of a selective beta-blocking agent (betaxolol) and a topical carbonic anhydrase inhibitor (dorzolamide), sufficient to significantly lower intraocular pressure (IOP), have similar or disparate impact on the retinal and retrobulbar circulation [21].
• Patients receiving 2% pilocarpine had the highest rate of discontinuation due to a clinical adverse experience, and the use of dorzolamide was not associated with systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors [22].
• PURPOSE: To evaluate the effect of dorzolamide 2% and latanoprost 0.005% on intraocular pressure (IOP) after small incision cataract surgery [23].

Gene context of dorzolamide

• In order to prove that the tail (in this case the picolinoyl moiety) conferring water solubility to a sulfonamide CA inhibitor is critically important for its topical effectiveness, similarly to the ring to which the sulfonamido group is grafted, we also prepared a dorzolamide derivative to which the picolinoyl moiety was attached [24].
• This new compound is more water soluble than dorzolamide (as hydrochloride salt), behaves as a strong CA II inhibitor and acts similarly to the parent derivative in lowering IOP in experimental animals [25].
• Topiramate, ethoxzolamide and benzolamide showed subnanomolar hCA VII inhibitory activity, whereas acetazolamide, methazolamide, dorzolamide and brinzolamide showed K(I)-s in the range of 2.1-3.5 nM [26].
• Furthermore, oral ACZ is reported to be more physiologically effective than 2% dorzolamide hydrochloride administered topically, even though in isolated tissues dorzolamide appears to be the most active as it shows the lowest IC(50) values for CA-II and CA-IV [M.F. Surgue, J. Ocular Pharmacol. Ther. 12 (1996) 363-376] [27].
• The disposition of dorzolamide, a carbonic anhydrase-II (CA-II) inhibitor, was examined in rats after oral and iv administration of 0.05, 0.5, 5, and 25 mg/kg [28].

Analytical, diagnostic and therapeutic context of dorzolamide

• Topically applied dorzolamide penetrates directly to the posterior segment of the eye and its presence is consistent with the initial report that dorzolamide increases retinal blood flow velocity in patients with normal tension glaucoma [7].
• Intravenous injections of 500 mg dorzolamide increased ONP(O)2 from 16.4+/-6.1 mm Hg to 26.9+/-12.2 mm Hg, or 52.5%+/-21.2% (n = 5; P = 0.017) [29].
• Ultratrace analysis of drugs in biological fluids using affinity probe capillary electrophoresis: analysis of dorzolamide with fluorescently labeled carbonic anhydrase [30].
• One eye in the dorzolamide group, 1 eye in the latanoprost group, and 4 eyes in the control group had an IOP of 30 mm Hg or higher 6 hours postoperatively [23].
• Aqueous humor formation after treatment with 3.5 microg timolol + 1.0 mg dorzolamide was decreased in treated vs. control eyes, after four days and was suppressed in both treated and control eyes after four weeks of treatment, but not when PG was added [31].

References