Abstract • The multiple-dose twice-daily efficacy of the topical carbonic anhydrase inhibitor MK-927, a racemic compound, was compared with that of its pharmacologically more active S-enantiomer in a four-center, double-masked, randomized, placebo-controlled, parallel study of 1.8% sezolamide hydrochloride (MK-417), 2% MK-927, and placebo, given twice daily to 48 patients with bilateral primary open angle glaucoma or ocular hypertension and morning intraocular pressure greater than 24 mm Hg in both eyes following washout of ocular hypotensive medications. Parallel 10-hour modified diurnal curves were performed before the study and on day 14, with 4-hour curves on days 1 and 4. Both compounds demonstrated significant lowering of intraocular pressure at 8 AM, 12 hours following the evening dose, and through 10 and 6 hours following the 8 AM dose for sezolamide and MK-927, respectively. Morning trough (evening) activity as measured by mean percent change in intraocular pressure from prestudy was 9.2% for sezolamide and −11.1% for MK-927 (−13.5% and −9.6%); peak effect occurred 2 hours after dose administration and was −19.4% and −19.2% for sezolamide and MK-927, respectively. From 2 hours after dose administration, sezolamide consistently demonstrated a slightly greater decrease in intraocular pressure than MK-927; however, these differences were not statistically significant. References 1. Ponticello GS, Freedman MB, Habecker CN, et al. Thienothiopyran-2-sulfonamides: a novel class of water-soluble carbonic anhydrase inhibitors . J Med Chem . 1987;30:591-597.Crossref 2. Baldwin JJ, Ponticello GS, Sugrue MF, et al. MK-927, a water soluble, topically effective carbonic anhydrase inhibitor. Presented at the Third Chemical Congress of North America; June 5,1988; Toronto, Ontario. 3. Baldwin JJ, Ponticello GS, Murcko M, et al. Three-dimensional structure of the carbonic anhydrase inhibitor complex derived from human carbonic anhydrase II and the optical isomers of MK-927 . Invest Ophthal Vis Sci . 1989;30( (suppl) ):374. 4. Baldwin J, Ponticello G, Anderson P, et al. Thienothiopyran-2-sulfonamides: novel topically active carbonic anhydrase inhibitors for the treatment of glaucoma . J Med Chem . 1989;32:2510-2513.Crossref 5. Wistrand PJ, Garg LC. Evidence of a highactivity C type of carbonic anhydrase in human ciliary processes . Invest Ophthal Vis Sci . 1979;18:802-806. 6. Sugrue MF, Gautheron P, Grove J, et al. MK-927: a topically effective ocular hypotensive carbonic anhydrase inhibitor . J Ocular Pharmacol . 1990;6:9-22.Crossref 7. Maren TH, Bar-Ilan A, Conroy CW, Brechue WF. Chemical and pharmacological properties of MK-927, a sulfonamide carbonic anhydrase inhibitor that lowers intraocular pressure by the topical route . Exp Eye Res . 1990;50:27-36.Crossref 8. Wang R-F, Serle JB, Podos SM, Sugrue MF. The effect of MK-927, a topical carbonic anhydrase inhibitor on IOP in glaucomatous monkeys . Curr Eye Res . 1990;9:163-168.Crossref 9. Maren TH. Carbonic anhydrase: general perspectives and advances in glaucoma research . Drug Dev Res . 1987;10:255-276.Crossref 10. Lippa EA. Topical carbonic anhydrase inhibitors. In: Dodgson S, ed. The Carbonic Anhydrases: Cellular Physiology and Molecular Genetics. New York, NY: Plenum Press. In press. 11. Lippa EA, Von Denffer HA, Hofmann HM, Brunner-Ferber FL. Local tolerance and activity of MK-927, a novel topical carbonic anhydrase inhibitor . Arch Ophthalmol . 1988;106:1694-1696.Crossref 12. Bron AM, Lippa EA, Hofmann HM, et al. MK-927: a topically effective carbonic anhydrase inhibitor in patients . Arch Ophthalmol . 1989;107:1143-1146.Crossref 13. Pfeiffer N, Hennekes R, Lippa EA, et al. MK-927: single-dose efficacy of a novel topical carbonic anhydrase inhibitor . Br J Ophthalmol . 1990;74:405-408.Crossref 14. Higginbotham EJ, Kass MA, Lippa EA, Batenhorst RL, Panebianco DL, Wilensky JT. MK-927: a topical carbonic anhydrase inhibitor: dose response and duration of action . Arch Ophthalmol . 1990;108:65-68.Crossref 15. Tuulonen A, Høvding G, Gustad L, et al. Multiple-dose dose-response curve of the topical carbonic anhydrase inhibitor MK-927 . Invest Ophthalmol Vis Sci . 1989;30( (suppl) ):24. 16. Buclin T, Lippa EA, Biollaz J, et al. Absence of metabolic effects of the novel topically active carbonic anhydrase inhibitor MK-927 and its Sisomer during a two-week ocular administration . Eur J Clin Pharmacol . 1989;36( (suppl) ):A188. 17. Pfeiffer N, Gerling J, Lippa EA, Brunner-Ferber F, Grehn F. Topical carbonic anhydrase inhibitors MK-927 and MK-417 have good local tolerability. Presented at the Glaucoma Symposium, XXVI International Congress of Ophthalmology; March 17,1990; Singapore. 18. Diestelhorst M, Bechetoille A, Lippa EA, Brunner-Ferber F, Krieglstein GK. Comparative potencies of the topical carbonic anhydrase inhibitors MK-417 and MK-927 . Invest Ophthalmol Vis Sci . 1989;30( (suppl) ):23. 19. Pfeiffer N, Greve E, Bechetoille A, et al. Additive wirkung von timolol und dem lokalen carboanhydrasehemmer MK-417. Presented at Deutschen Ophthalmologischen Gesellschaft; September 25, 1990; Baden-Baden, Federal Republic of Germany. 20. Lippa EA, Sherwood M, Laibovitz RM, et al. MK-417 vs timolol: comparative activity . Invest Ophthalmol Vis Sci . 1990;31( (suppl) ):232.
Archives of Ophthalmology – American Medical Association
Published: Jan 1, 1991
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