MK-507 (L-671,152), a topically active carbonic anhydrase inhibitor, reduces aqueous humor production in monkeys.
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.
Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY.
R F
RF
Wang
J B
JB
Serle
S M
SM
Podos
M F
MF
Sugrue
D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D005260:Female; D015590:Fluorophotometry; D007429:Intraocular Pressure / Q000187:drug effects; D008252:Macaca fascicularis; D013449:Sulfonamides / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D014065:Tonometry, Ocular
D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; C062765:dorzolamide