The ocular hypotensive effect of the topical carbonic anhydrase inhibitor L-671,152 in glaucomatous monkeys.
L-671,152, a new potent water-soluble inhibitor of human carbonic anhydrase II in vitro, was applied topically to cynomolgus monkey eyes in which glaucoma had been produced by argon laser photocoagulation of the trabecular mesh-work. Intraocular pressure was measured at 0 hours, 0.5 hours, and hourly for 8 hours in eight eyes for 2 baseline days, 1 day receiving the vehicle and 5 days receiving therapy with 2% L-671,152 twice a day, after initial single-dose trials of various concentrations. Intraocular pressure was not significantly different comparing baseline and vehicle-treated days. Significant intraocular pressure reductions occurred from 1 to 8 hours after the first dose, and lasted for at least 16 hours after the second dose. The reduction in intraocular pressure became more pronounced from day 1 to day 5 at each time interval. The mean (+/- SEM) maximum reduction in intraocular pressure was 7.8 +/- 2.1 mm Hg on day 1 and 10.1 +/- 2.4 mm Hg on day 5 at 3 hours after administration, comparing the intraocular pressure in drug-treated and vehicle-treated eyes. L-671,152 has a longer duration of action than does previously studied MK-927 in glaucomatous monkeys. It appears to have great clinical potential.
Wang
R F
RF
Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029.
Serle
J B
JB
Podos
S M
SM
Sugrue
M F
MF
D000287:Administration, Topical; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000601:surgery; D007429:Intraocular Pressure / Q000187:drug effects*; D053685:Laser Therapy; D008252:Macaca fascicularis; D015394:Molecular Structure; D013449:Sulfonamides / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; C062765:dorzolamide