May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Precinical Efficacy Of Al–12182, A Selective Fp Prostaglandin Analog
Author Affiliations & Notes
  • M.R. Hellberg
    Medicinal Chemistry,
    Alcon Laboratories, Fort Worth, TX
  • R. Selliah
    Medicinal Chemistry,
    Alcon Laboratories, Fort Worth, TX
  • M. McLaughlin
    Pharmacology,
    Alcon Laboratories, Fort Worth, TX
  • V. Sallee
    Medicinal Chemistry,
    Alcon Laboratories, Fort Worth, TX
  • N. Sharif
    Molecular Pharmacology,
    Alcon Laboratories, Fort Worth, TX
  • T. Dean
    Glaucoma Research,
    Alcon Laboratories, Fort Worth, TX
  • Footnotes
    Commercial Relationships  M.R. Hellberg, Alcon Laboratories E; R. Selliah, Alcon Laboratories E; M. McLaughlin, Alcon Laboratories E; V. Sallee, Alcon Laboarties E; N. Sharif, Alcon Laboratories E; T. Dean, Alcon Laboratories E.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 2087. doi:
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      M.R. Hellberg, R. Selliah, M. McLaughlin, V. Sallee, N. Sharif, T. Dean; Precinical Efficacy Of Al–12182, A Selective Fp Prostaglandin Analog . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2087.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: To characterize the in vitro binding and functional activity of AL–12180 (carboxylic acid of AL–12182) and the in vivo efficacy and side effects profile of AL–12182. Methods: Prostaglandin (PG) affinity and/or functional activity assay(s) were used to determine activity at FP, EP, DP, TP and IP receptors. Local effects on ocular tissue were studied in New Zealand albino rabbits (NZA) using a standardized scale for hyperemia. The IOP effects were studied in the conscious ocular hypertensive (laser– induced glaucoma) monkey model. Results: The binding affinity (Ki) of AL–12180 at the FP receptor is 147 nM vs. 92 nM for latanoprost acid. AL–12180 is a full agonist in the FP receptor functional assay (EC50 = 24 nM) with low (micromolar) affinity for EP, DP, IP and TP receptors. AL–12182 produced a low incidence of ocular hyperemia at doses up to 30 micrograms in NZA rabbits. Single doses of 0.3, 1.0 and 3.0 micrograms afforded peak reductions in IOP of 13.7, 22.1 and 30.8% in the lasered eye of cynomolgus monkeys. Peak reductions of 22.1, 23.1, and 39.7% occurred following b.i.d. dosing of 0.3, 1.0 and 3.0 micrograms for 3 days. Conclusions: The results of the preclinical evaluation of AL–12182 demonstrate that it is a selective PG analog with outstanding efficacy and a low propensity to cause ocular hyperemia.

Keywords: pharmacology • receptors: pharmacology/physiology • intraocular pressure 
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