L-662,583 demonstrated strong inhibitory effects on human red blood cell carbonic anhydrase II in laboratory tests, with an IC50 value of 0.7 nM, outperforming
MK-927,
acetazolamide, and
methazolamide which had IC50 values of 13.0 nM, 10.8 nM, and 21.2 nM respectively. In an ex vivo study using albino rabbits, a 50 μl drop of a 0.1% L-662,583 solution applied for 1 hour resulted in a 63% inhibition of carbonic anhydrase activity in the iris and ciliary body, surpassing the 30% and 20% inhibitions caused by similar treatments with acetazolamide and methazolamide.
High-performance liquid chromatography was used to determine L-662,583 concentrations in the cornea, aqueous humor, and iris plus ciliary body of albino rabbits at specific times after applying a single drop of a 2% solution. Peak levels were observed at 0.5 hours for the cornea (47.4 μg/g), 2 hours for the aqueous humor (4.51 μg/ml), and 1 hour for the iris plus ciliary body (9.61 μg/g).
In rabbits with artificially elevated intraocular pressure caused by α-chymotrypsin injection, L-662,583 reduced pressure by 4.5 mmHg, 6.2 mmHg, and 9.8 mmHg following the application of 0.01%, 0.1%, and 0.5% solutions, respectively. These effects were observed from 1 to 5 hours post-application. The unilateral application of L-662,583 did not affect the untreated eye, indicating a localized effect. Normotensive rabbits were less responsive to the pressure-lowering effects of L-662,583, with a 2% solution reducing pressure by only 2.3 mmHg.
In cynomolgus monkeys with induced
ocular hypertension, a single drop of 2% L-662,583 significantly reduced intraocular pressure by a maximum of 8.3 mmHg at 3 hours, a 23% reduction from the baseline. The normotensive eyes of the monkeys were more resistant to the hypotensive effects of L-662,583 compared to hypertensive eyes, with a 2% solution reducing pressure by 2.4 mmHg at 2 hours.
L-662,583, structurally distinct from MK-927, is a water-soluble carbonic anhydrase inhibitor that lowers intraocular pressure when applied topically, with its effects being localized within the eye, similar to MK-927.
How to Use Synapse Database to Search and Analyze Translational Medicine Data?
The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

Click on the image below to go directly to the Translational Medicine search interface.
