The hydrolysis of the prostaglandin analog prodrug bimatoprost to 17-phenyl-trinor PGF2alpha by human and rabbit ocular tissue.

  title={The hydrolysis of the prostaglandin analog prodrug bimatoprost to 17-phenyl-trinor PGF2alpha by human and rabbit ocular tissue.},
  author={Mark R. Hellberg and T L Ke and Karen S. Haggard and Peter G. Klimko and Tom R Dean and Gustav Graff},
  journal={Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
  volume={19 2},
  • M. Hellberg, T. Ke, +3 authors G. Graff
  • Published 2003
  • Chemistry, Medicine
  • Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
Bimatoprost (Lumigan), the ethyl amide derivative of the potent prostaglandin FP agonist 17-phenyl-trinor PGF(2alpha), has been reported to be a member of a pharmacologically unique class of ocular hypotensive agents. To confirm that bimatoprost, which is intrinsically active as an FP prostaglandin agonist, is also a prostaglandin analog prodrug, the hydrolysis of bimatoprost by ocular tissues was studied by incubating solutions containing bimatoprost with either human or rabbit ocular tissue… Expand
Update and commentary on the pro-drug bimatoprost and a putative ‘prostamide receptor’
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
Bimatoprost and prostaglandin F(2 alpha) selectively stimulate intracellular calcium signaling in different cat iris sphincter cells.
The selective stimulation of different cells in the same cat iris sphincter preparation by bimatoprost and prostaglandin F(2 alpha), along with the complete absence of observed instances in which the same cells respond to both agonists, strongly suggests the involvement of distinct receptors for prostaglandsin F (2 alpha) and bim atoprost. Expand
Bimatoprost, the prodrug of a prostaglandin analogue.
This important study confirms the results found in previous studies and concludes that BP is not a prodrug and acts directly as an amide to reduce intraocular pressure (IOP) after topical application of FP receptor agonists, including BP. Expand
Intraocular Pressure-Lowering Activity of NCX 470, a Novel Nitric Oxide-Donating Bimatoprost in Preclinical Models.
NCX 470 lowers IOP more than equimolar bimatoprost in three animal models of glaucoma by activating PGF2α and NO/cGMP signaling pathways. Expand
Bimatoprost: a novel antiglaucoma agent.
Extensive ocular distribution/metabolism studies in non-human primates demonstrate that bimatoprost is not a prodrug, it remains essentially intact, and its profound ocular hypotensive effects may, therefore, be attributed to its prostamide-mimetic properties. Expand
Esterase activity in porcine and albino rabbit ocular tissues
Differences in esterase activities among the ocular tissues and the species are revealed, and basic knowledge on ocular esterases provides background information particularly for posterior segment drug development. Expand
Ocular hypotensive FP prostaglandin (PG) analogs: PG receptor subtype binding affinities and selectivities, and agonist potencies at FP and other PG receptors in cultured cells.
In conclusion, travoprost acid has the highest affinity, the highest FP-receptor-selectivity, and the highest potency at the FP receptor as compared to the other ocular hypotensive PG analogs known so far, including free acids of latanoprost, bimatobrost, and unoprostone isopropyl ester. Expand
Activation of the prostanoid FP receptor inhibits adipogenesis leading to deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy.
Prostaglandin analogues have the potential to inhibit adipogenesis through FP receptor stimulation and may directly lead to reduced orbital fat by inhibiting adipogenesis. Expand
Cat iris sphincter smooth-muscle contraction: comparison of FP-class prostaglandin analog agonist activities.
These data confirm the presence of functional FP-receptors in the cat iris sphincter, which are exquisitely well coupled and which respond to a variety of FP-class prostaglandin analogs with differing potencies. Expand
Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes
An improvement in the pharmacokinetic parameters of ISV-215 may provide a better platform to optimize a bimatoprost formulation that offers the same degree of efficacy in lowering intraocular pressure and improved therapeutic index in glaucomatous patients by lessening the ocular side effects associated with long-term use of topical prostaglandin F2α analogs. Expand


3-Oxa-15-cyclohexyl prostaglandin DP receptor agonists as topical antiglaucoma agents.
A series of prostaglandin DP agonists containing a 3-oxa-15-cyclohexyl motif was synthesized and evaluated in several in vitro and in vivo biological assays, finding that selected amide prodrugs of the carboxylic acid enhance in vivo potency, presumably by increasing bioavailability. Expand
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.
Clinical studies show that travoprost 0.004% (isopropyl ester) provided intraocular pressure control superior to timolol 0.5% when used as monotherapy in patients with open-angle glaucoma or ocular hypertension, and AL-6598 0.01% provided a sustained intraocular Pressure reduction with q.i.d. application. Expand
Bimatoprost and its free acid are prostaglandin FP receptor agonists.
Bimatoprost displaced [3H]prostaglandin F(2alpha) from FP receptors and rapidly mobilized intracellular Ca(2+) through cloned human FP receptors expressed in human embryonic kidney cells and via native FP receptors in 3T3 mouse fibroblasts. Expand
Nepafenac, a Unique Nonsteroidal Prodrug with Potential Utility in the Treatment of Trauma-Induced Ocular Inflammation: II. In Vitro Bioactivation and Permeation of External Ocular Barriers
The enhanced permeability of nepafenac, combined with rapid bioactivation to amfenac by the iris/ciliary body and retina/choroid, make it a target specific NSAID for inhibiting prostaglandin formation in the anterior and posterior segments of the eye. Expand
The pharmacology of bimatoprost (Lumigan).
A single dose of bimatoprost markedly reduces intraocular pressure in dogs and laser-induced ocular hypertensive monkeys, and Decreases in intraocular Pressure are well maintained for at least 24 hr post-dose. Expand