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.

@article{Hellberg2002IdentificationAC,
  title={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.},
  author={M. Hellberg and M. Mclaughlin and N. Sharif and L. Desantis and T. Dean and E. P. Kyba and J. Bishop and P. Klimko and P. W. Zinke and Robert D. Selliah and G. Barnes and J. Defaller and A. Kothe and T. Landry and E. Sullivan and R. Andrew and A. Davis and L. Silver and M. Bergamini and S. Robertson and A. Weiner and V. Sallee},
  journal={Survey of ophthalmology},
  year={2002},
  volume={47 Suppl 1},
  pages={
          S13-33
        }
}
The structure-activity studies that led to the identification of travoprost, a highly selective and potent FP prostaglandin analog, and AL-6598, a DP prostaglandin analog, are detailed. In both series, the 1-alcohol analogs are very effective and are thought to be acting as prodrugs for the biologically active carboxylic acids. The efficacy of amide prodrugs depends on the degree of substitution and the size of the substituents. Selected compounds are profiled in vitro and in vivo preclinically… Expand
Preclinical efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist.
  • M. Hellberg, V. Sallee, +4 authors P. W. Zinke
  • Medicine
  • Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
  • 2001
TLDR
Topical application of travoprost was well tolerated in rabbits, cats and monkeys, causing no ocular irritation or discomfort at doses up to 1 microg, and has the ocular hypotensive efficacy of PGF2alpha isopropyl ester but with less severe ocular side effects. Expand
Clinical utility and differential effects of prostaglandin analogs in the management of raised intraocular pressure and ocular hypertension
TLDR
The vast majority of clinical trials demonstrate IOP-lowering superiority of latanoprost, bimatoprost and travoprost compared with timolol 0.5%, brimonidine 0.2%, or dorzolamide 2% monotherapy. Expand
15-Fluoro prostaglandin FP agonists: a new class of topical ocular hypotensives.
TLDR
Evaluation of selected ester prodrugs of these 15-fluoro prostaglandins in vivo highlighted their generally low propensity to elicit hyperemia or ocular irritation in rabbits and efficacious intraocular pressure-lowering property in monkeys. Expand
Update and commentary on the pro-drug bimatoprost and a putative ‘prostamide receptor’
TLDR
An update on the discovery of potent and efficacious intraocular pressure (IOP)-lowering FP-class prostaglandin (PG) analogs is provided and published data is discussed that addresses the debate in this arena. Expand
Preclinical pharmacology of AL-12182, a new ocular hypotensive 11-oxa prostaglandin analog.
  • N. Sharif, M. Mclaughlin, +4 authors J. L. Parker
  • Medicine
  • Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
  • 2006
TLDR
AL-12180 is a relatively potent and selective FP-receptor agonist whose isopropyl ester prodrug lowers IOP by as much as 40% following topical ocular dosing in a laser-induced nonhuman primate model of ocular hypertension. Expand
Pharmacological mechanisms, clinical effectiveness, and side-effects of prostaglandin analogues as anti-glaucoma agents
TLDR
The mechanisms of action of PG-related ophthalmic solutions are compared, the adverse effects and their mechanisms are reviewed, and measures to prevent them are established. Expand
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TLDR
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TLDR
FR-190997 is an unexampled efficacious ocular hypotensive B2-receptor non-peptide BK agonist that activates multiple signaling pathways to cause IOP reduction of conscious ocular hypertensive cynomolgus monkey eyes. Expand
Prostanoid receptor agonists for glaucoma treatment
  • M. Aihara
  • Medicine
  • Japanese Journal of Ophthalmology
  • 2021
TLDR
This review will trace the history and development of FP and EP2 receptor agonists from their original function, and explain their potential as first-line drugs including elucidation of their efficacy and safety. Expand
AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist.
  • N. Sharif, M. Mclaughlin, C. Kelly
  • Medicine
  • Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
  • 2007
TLDR
AL-34662 is a high-affinity 5-HT2 receptor agonist that potently mobilizes [Ca2+]i in h-CM and h-TM cells, and which efficaciously lowers intraocular pressure in conscious ocular hypertensive cynomolgus monkey eyes through a local effect with minimal side-effects. Expand
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References

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Preclinical efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist.
  • M. Hellberg, V. Sallee, +4 authors P. W. Zinke
  • Medicine
  • Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
  • 2001
TLDR
Topical application of travoprost was well tolerated in rabbits, cats and monkeys, causing no ocular irritation or discomfort at doses up to 1 microg, and has the ocular hypotensive efficacy of PGF2alpha isopropyl ester but with less severe ocular side effects. Expand
Structure-activity relationships and receptor profiles of some ocular hypotensive prostanoids.
TLDR
One of the analogues of prostaglandin F, 13,14-dihydro-17-phenyl-18,19,20-trinor PGF2 alpha-isopropyl ester (latanoprost), has been found in clinical studies to be a highly potent and efficacious IOP-reducing agent for the treatment of glaucoma. Expand
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In studying prostaglandin analogs, it was found that a diverse variety of prostanoid receptor selective agonists lowered intraocular pressure in dogs and/or monkeys. Expand
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The results indicate that although PGD2 and BW245C are effective in reducing human IOP, their clinical usefulness as anti-glaucoma drugs may be limited by the extraocular side effects. Expand
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Both the ocular hypotensive actions and the conjunctival pathology of PGD2 may be replicated individually by employing PGD1 analogues and metabolites by employing selective DP-receptor agonists. Expand
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Findings reinforce the concept that selective DP receptor agonists may be useful for lowering intraocular pressure without causing ocular surface pathology and suggest a possible subdivision of the DP receptor designation. Expand
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The phenyl-substituted PGF2 alpha analogues exhibited good intraocular pressure reducing effect, were more selective, and exhibited a much higher therapeutic index in the eye than PGF 2 alpha or its isopropyl ester. Expand
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TLDR
PGE2 was the strongest in causing these side effects, followed by PGF2 alpha, and PGD2 did not cause any of these responses except for some development of conjunctival hyperemia. Expand
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TLDR
The results of this study suggest that PGE2, or a derivative, may offer a new class of topically effective ocular hypotensive agents useful in lowering the intraocular pressure of glaucoma patients. Expand
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TLDR
The results clearly show that the DP receptors in rabbit and cat eyes are involved in intraocular pressure regulation, however, under baseline conditions DP receptor activity does not contribute to this regulation. Expand
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