May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
PROSTANOID EP4 RECEPTOR STIMULATION PRODUCES PROFOUND OCULAR HYPOTENSION THAT INVOLVES PRESSURE DEPENDENT OUTFLOW
Author Affiliations & Notes
  • A.B. Kharlamb
    Biological Sciences,
    Allergan Inc, Irvine, CA
  • A.H. Krauss
    Biological Sciences,
    Allergan Inc, Irvine, CA
  • J. Chen
    Biological Sciences,
    Allergan Inc, Irvine, CA
  • D.F. Woodward
    Biological Sciences,
    Allergan Inc, Irvine, CA
  • A.L. Nieves
    Biological Sciences,
    Allergan Inc, Irvine, CA
  • T. Dinh
    Biological Sciences,
    Allergan Inc, Irvine, CA
  • R.M. Burk
    Chemical Sciences,
    Allergan Inc, Irvine, CA
  • M. Holoboski
    Chemical Sciences,
    Allergan Inc, Irvine, CA
  • M. Posner
    Chemical Sciences,
    Allergan Inc, Irvine, CA
  • S.F. E. Nilsson
    Dept of Medicine & Care, Pharmacology, University of Linkoping, Linkoping, Sweden
  • Footnotes
    Commercial Relationships  A.B. Kharlamb, Allergan Inc E; A.H. Krauss, Allergan Inc E; J. Chen, Allergan Inc E; D.F. Woodward, Allergan Inc E; A.L. Nieves, Allergan Inc E; T. Dinh, Allergan Inc E; R.M. Burk, Allergan Inc E; M. Holoboski, Allergan Inc E; M. Posner, Allergan Inc E; S.F.E. Nilsson, Allergan Inc F.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 1035. doi:
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      A.B. Kharlamb, A.H. Krauss, J. Chen, D.F. Woodward, A.L. Nieves, T. Dinh, R.M. Burk, M. Holoboski, M. Posner, S.F. E. Nilsson; PROSTANOID EP4 RECEPTOR STIMULATION PRODUCES PROFOUND OCULAR HYPOTENSION THAT INVOLVES PRESSURE DEPENDENT OUTFLOW . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1035.

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

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Abstract

Abstract: : Purpose: To investigate the ocular hypotensive effects of the selective EP4 receptor agonist ONO–123A and its effects on aqueous humor dynamics. Methods: Intraocular pressure (IOP) was measured in laser–induced ocular hypertensive monkeys and ocular normotensive beagle dogs. Ocular surface hyperemia was visually assessed in dogs and graded mild, moderate or severe. Pressure–dependent aqueous humor outflow was determined by the two–level perfusion method. Results: ONO–AEI–329 and an esterified derivative thereof produced a profound decrease in monkey IOP. Single doses in the 0.01 – 0.1% range reduced IOP to the level of the normotensive, vehicle–treated contralateral eye. Such reductions were in the vicinity of 50%. A similar, profound decrease in IOP was found in dogs, where ocular hypotension was accompanied by moderately severe ocular surface redness. No miosis was detected in either species. In monkeys a single topical 0.01 % dose increased outflow facility by 43%. Conclusions:EP4 receptor agonists offer novel anti–glaucoma drugs that directly enhance pressure–dependent outflow. The ocular hypotensive activity is marked and appears to normalize elevated IOP, similar to EP–2 receptor agonists. EP2 and EP4 receptors appear to represent promising targets for the design of future anti–glaucoma drugs.

Keywords: eicosanoids • intraocular pressure • intraocular pressure 
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