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].
Dorzolamide HCl/盐酸多佐胺 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CH22 cells
50 µM
48 hours
Inhibited chordoma cell proliferation and migration
Neuro Oncol. 2021 Oct 1;23(10):1709-1722.
U-CH1 cells
50 µM
48 hours
Inhibited chordoma cell proliferation and migration
Neuro Oncol. 2021 Oct 1;23(10):1709-1722.
Bone marrow monocytes (BMMs)
3.125 µM to 200 µM
7 days
Inhibited osteoclast differentiation
Neuro Oncol. 2021 Oct 1;23(10):1709-1722.
Dorzolamide HCl/盐酸多佐胺 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Long-Evans rats
Diabetes model
Intravenous injection
15 mg/kg
Single injection
To investigate the effect of Dorzolamide on retinal pH regulation in diabetic rats. Results showed that Dorzolamide dramatically increased retinal acidity in both control and diabetic retinas to a similar degree, but in diabetics, the effect tended to increase with time and after 2 hours could be two to three times larger than at the beginning.
Invest Ophthalmol Vis Sci. 2019 Feb 1;60(2):723-730
DBA/2J mice
Glaucoma model
Topical application
2%
Single dose, observed at 1 and 2 hours post-administration
To test the hypothesis that acute topical dorzolamide decreases intraocular pressure (IOP) and increases retinal and choroidal blood flow in the DBA/2J Mice model of glaucoma. Results showed that dorzolamide significantly lowered IOP and increased retinal and choroidal blood flow in older DBA/2J mice.
Invest Ophthalmol Vis Sci. 2016 Mar;57(3):826-31
DBA/2J mice
Glaucoma model
Topical application
2%
Single dose, effects measured at 1 and 2 hours post-application
To test the hypothesis that acute topical dorzolamide decreases intraocular pressure and increases retinal and choroidal blood flow in the DBA/2J Mice model of glaucoma. Results showed that dorzolamide lowered IOP and increased retinal and choroidal blood flow in older DBA/2J mice.
Invest Ophthalmol Vis Sci. 2016 Mar;57(3):826-31
New Zealand albino rabbits
Anesthetized rabbit model
Topical application
2%, 50 μL
Single dose, observed for 120 minutes
To determine the effects of dorzolamide on choroidal and ciliary blood flow and aqueous production. Results showed that dorzolamide lowered IOP by 19% and aqueous flow by 17%, increased ciliary blood flow by 18%, but had no significant effect on choroidal blood flow.
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