Survey of Ophthalmology
Volume 47 , Pages S13-S33 , August 2002

Identification and Characterization of the Ocular Hypotensive Efficacy of Travoprost, a Potent and Selective FP Prostaglandin Receptor Agonist, and AL-6598, a DP Prostaglandin Receptor Agonist

  • Mark R. Hellberg, PhD

      Affiliations

    • Corresponding Author InformationReprint address: Mark Hellberg, Alcon Research Ltd. 6201 South Freeway, Fort Worth, TX, 76134, USA
    • Departments of Medicinal Chemistry, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Marsha A. McLaughlin, PhD

      Affiliations

    • Departments of In Vivo Pharmacology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Naj A. Sharif, PhD

      Affiliations

    • Departments of Molecular Pharmacology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Louis DeSantis, PhD

      Affiliations

    • Departments of Glaucoma Research, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Tom R. Dean, PhD

      Affiliations

    • Departments of Medicinal Chemistry, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Evan P. Kyba, PhD

      Affiliations

    • Departments of Medicinal Chemistry, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • John E. Bishop, PhD

      Affiliations

    • Departments of Medicinal Chemistry, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Peter G. Klimko, PhD

      Affiliations

    • Departments of Medicinal Chemistry, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Paul W. Zinke, PhD

      Affiliations

    • Departments of Medicinal Chemistry, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Robert D. Selliah, PhD

      Affiliations

    • Departments of Medicinal Chemistry, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • George Barnes, PhD

      Affiliations

    • Departments of In Vivo Pharmacology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Joseph DeFaller, PhD

      Affiliations

    • Departments of Clinical Ophthalmology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Angela Kothe, PhD

      Affiliations

    • Departments of Clinical Ophthalmology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Theresa Landry, PhD

      Affiliations

    • Departments of Clinical Ophthalmology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • E.Kenneth Sullivan, PhD

      Affiliations

    • Departments of Biostatistics, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Russell Andrew, MS

      Affiliations

    • Departments of Biostatistics, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Alberta A. Davis, PhD

      Affiliations

    • Departments of Clinical Ophthalmology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Lewis Silver, PhD

      Affiliations

    • Departments of Clinical Ophthalmology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Michael V.W. Bergamini, PhD

      Affiliations

    • Departments of Clinical Ophthalmology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Stella Robertson, PhD

      Affiliations

    • Departments of Clinical Ophthalmology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Alan L. Weiner, PhD

      Affiliations

    • Departments of Clinical Ophthalmology, Alcon Research Ltd., Fort Worth, TX, USA
  • ,
  • Verney L. Sallee, PhD

      Affiliations

    • Departments of In Vivo Pharmacology, Alcon Research Ltd., Fort Worth, TX, USA

References 

  1. Alm A, Villmsen J. Effects of topically applied PGF and its isopropyl ester on normal and glaucomatous human eyes. In:  Bito L,  Stjernschantz J editor. The Ocular Effects of Prostaglandins and Other Eicosanoids. New York: Alan Liss Inc; 1989;p. 447–458
  2. Bito LZ, Baroody RA. The ocular pharmacokinetics of eicosanoids and their derivatives 1. Comparison of ocular eicosanoid penetration and distribution following the topical application of PGF, PGF 1-methyl ester and PGF2a α-1-isopropyl ester. Exp Eye Res. 1987;44:217–226
  3. Crider JY, Griffin BW, Sharif NA. Prostaglandin DP receptors positively coupled to adenylyl cyclase in embryonic bovine tracheal (EBTr) cells (pharmacological characterization using agonists and antagonists). Br J Pharmacol. 1999;127:204–210
  4. Crider JY, Xu SX, Griffin BW, Sharif NA. Use of a semi-automated, robotic radioimmunoassay to measure cAMP generated by activation of DP-, EP2- and IP-prostaglandin receptors in human ocular and other cell-types. Prostaglandins Leukotrienes & Essential Fatty Acids. 1998;59:77–82
  5. Flach A, Eliason J. Topical prostaglandin E2 effects on normal human intraocular pressure. J Ocular Pharm. 1988;4:13–18 [Published erratum appears in J Ocul Pharmacol 7:189, 1991 which correctly identifies the compound evaluated as EP analog RS-18492]
  6. Goh Y, Nakajim M, Azuma I, Hayashi O. Effects of prostaglandin D2 and its analogues on intraocular pressure in rabbits. Jpn J Ophthalmol. 1988;32:471–480
  7. Goh Y, Nakajim M, Azuma I. Prostaglandin D2 reduces intraocular pressure. Br J Ophthalmol. 1988;72:461–464
  8. Guiffre G. The effects of prostaglandin F in the human eye. Graefes Arch Clin Exp Ophthalmol. 1985;222:139–141
  9. Hackett RB, McDonald TO. Eye irritation. In:  Marzulli FN,  Maibach HI editor. Dermatotoxicology. Washington DC: Hemisphere Publishing Corp; 1991;p. 299–306 ed 4,
  10. Hellberg MR, Sallee VL, McLaughlin MA, et al.  Preclinical efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist. J Ocul Pharmacol Ther. 2001;17:421–432
  11. Liljebris C, Solen G, Resul B, et al.  Derivatives of 17-phenyl-18,19,20-trinorprostaglandin F isopropyl ester (potential antiglaucoma agents). J Med Chem. 1995;38:289–304
  12. Matsugi T, Kageyama M, Nishimura K, et al.  Selective prostaglandin D2 receptor stimulation elicits ocular hypotensive effects in rabbits and cats. Eur J Pharmacol. 1995;275:245–249
  13. Nakajima M, Goh Y, Azuma Hayashi O. Effects of prostaglandin D2 and its analogue, BW245C on intraocular pressure in humans. Graefes Arch Clin Exp Opthalmol. 1991;229:411–413
  14. Netland PA, Landry T, Sullivan EK, et al.  Travoprost compared with latanoprost and timolol, in patients with open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 2001;132:472–484
  15. Resul B, Stjernschantz J, No K, et al.  Phenyl-substituted prostaglandins (potent and selective antiglaucoma agents). J Med Chem. 1993;36:243–248
  16. Resul B, Stjernschantz J, Selen G, Bito L. Structure-activity relationships and receptor profiles of some ocular hypotensive prostanoids. Surv Opthalmol. 1997;41(Suppl 2):S47–S52
  17. Schulz BG, Beckman R, Muller B, et al.  Cardio- and hemodynamic profile of selective PGD2 analogs. Adv Prostaglandin Thromboxane Leukotriene Res. 1991;21:591–594
  18. Sharif NA, Crider JY, Xu SX, Williams GW. Affinities, selectivities, potencies and intrinsic activities of natural and synthetic prostanoids using endogenous receptors (focus on DP class prostanoids). J Pharmacol Exp Ther. 2000;293:321–328
  19. Sharif NA, Davis TL, Williams GW. [3H]AL-5848 ([3H] 9β-(+)-Fluprostenol). Carboxylic acid of travoprost (AL-6221), a novel FP prostaglandin to study the pharmacology and autoradiographic location of the FP receptor. J Pharm Pharmacol. 1999;51:685–694
  20. Stjernschantz J, Resul B. Phenyl substituted prostaglandin analogues for glaucoma treatment. Drugs of the Future. 1992;17:691–704
  21. Stjernschantz J, Selen G, Sjoquist B, Resul R. Preclinical pharmacology of latanoprost, a phenyl-substituted PFG2 alpha analogue. Adv Prostaglandin Thromboxane Leukotriene Res. 1995;23:513–518
  22. Thierauch KH, Sturzebecher S, Schillinger E, et al.  Stable 9β or 11α halogen-15-cyclohexyl-prostaglandins with high affinity to the PGD2 receptor. Prostaglandins. 1988;35:855–868
  23. Waterbury L, Eglen R, Faurot G, Cooper G. EP3 but not EP2, FP, or TP prostanoid-receptor stimulation may reduce intraocular pressure. Invest Ophthalmol Vis Sci. 1990;31:2560–2567
  24. Woodward D, Chan M, Burke J, et al.  J Ocular Pharmacol Ther. 1994;10:177–193
  25. Woodward DF, Hawley SB, Williams LS, et al.  Studies on the ocular pharmacology of prostaglandin D2. Invest Ophthalmol Vis Sci. 1990;31:138–146
  26. Woodward DF, Spada CS, Hawley SB, et al.  Further studies on ocular responses to DP receptor stimulation. Eur J Pharmacol. 1993;230:327–333
  27. Zhan GF, Toris CB, Camras CB, et al.  A prostaglandin DP receptor agonist increases uveoscleral outflow in normotensive monkey eyes. Invest Ophthalmol Vis Sci (Suppl). 2001;42S:4502; [abstract]

PII: S0039-6257(02)00293-X

Survey of Ophthalmology
Volume 47 , Pages S13-S33 , August 2002