MK-507 (L-671,152), a topically active carbonic anhydrase inhibitor, reduces aqueous humor production in monkeys
R. F. Wang, J. B. Serle, S. M. Podos and M. F. Sugrue
Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY.
An investigation was carried out to determine the mechanism by which MK-507
(L-671,152), a water-soluble inhibitor of human carbonic anhydrase II in
vitro, reduces intraocular pressure when applied topically to monkey eyes.
Intraocular pressure, tonographically measured outflow facility, and
fluorophotometrically determined aqueous humor flow were measured before
and after therapy in eight normal cynomolgus monkeys. Fifty microliters of
2% MK-507 was instilled in one eye and diluent in the contralateral eye.
Baseline values for intraocular pressure, outflow facility, and aqueous
humor flow were similar in the drug-treated and diluent-treated control
eyes. After therapy, intraocular pressure was significantly (P less than
.05) reduced from 1 to 7 hours (eg, 14.0 +/- 1.0 and 15.9 +/- 0.9 mm Hg
[mean +/- SEM], treated and control eyes, respectively, at 3 hours).
Outflow facility was not significantly (P greater than .40) changed at 3
hours, and aqueous humor flow measured over 5 hours was significantly (P
less than .05) reduced (38%) in treated (0.9 +/- 0.1 microL/min) as
compared with control eyes (1.5 +/- 0.1 microL/min). The results suggest
that MK-507 reduces intraocular pressure by decreasing aqueous humor
production.
