Effect of Ticrynafen on Aqueous Humor Dynamics in Monkeys

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Abstract

Objective

To determine the effect of ticrynafen, a non-sulfhydryl-reactive compound similar to ethacrynic acid, on outflow facility in normotensive monkey eyes and on intraocular pressure (IOP) in monkey eyes with laser-induced glaucoma.

Methods

In normotensive eyes, facility (perfusion) was measured shortly before and after bolus or exchange intracameral infusion of ticrynafen or vehicle in opposite eyes, and 3.5 to 4.5 hours after 5 days of twice-daily 2% ticrynafen or vehicle ointment. In glaucomatous eyes, baseline and vehicle diurnal IOP curves were established, 2% ticrynafen ointment was given twice daily for 5 days, and IOP was measured immediately before and 0.5 to 6 hours after each morning treatment.

Results

In normotensive eyes, exchange 2-mL infusion of 0.2-, 1-, or 4-mmol/L ticrynafen increased facility by 33% +/- 6% (mean +/- SEM), 73% +/- 18%, and 60% +/- 11%, respectively. Day 5 posttreatment facility was higher in the ticrynafen group than in controls by 28% +/- 9%. In glaucomatous eyes, maximum IOP decline, from approximately 35 mm Hg, was 7.5 +/- 2.0 mm Hg on day 4 and 9.8 +/- 2.4 mm Hg on day 5 of twice-daily ticrynafen treatment.

Conclusion

The facility-increasing, IOP-lowering action of ticrynafen, ethacrynic acid, and derivatives may not depend entirely on sulfhydryl reactivity.

Clinical Relevance

Whether such drugs as ethacrynic acid and ticrynafen prove valuable for glaucoma therapy, at the least they are useful probes to study aqueous outflow mechanisms.

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