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1 General aspects (0)   1.1 Epidemiology (10)   1.2 Population genetics (7)   1.3 Pathogenesis (3)   1.4 Quality of life (3)   1.5 Glaucomas as cause of blindness (2)   1.6 Prevention and screening (5) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (0)   2.2 Cornea (1)   2.3 Sclera (0)   2.4 Anterior chamber angle (0)   2.5 Meshwork (3)     2.5.1 Trabecular meshwork (10)     2.5.2 Schlemms canal (0)     2.5.3 Scleral outlet channels (0)   2.6 Aqueous humor dynamics (0)     2.6.1 Production (0)     2.6.2 Outflow (1)       2.6.2.1 Trabecular meshwork (1)       2.6.2.2 Uveoscleral (0)     2.6.3 Compostion (3)   2.7 Episcleral veins and venous pressure (1)   2.8 Iris (4)   2.9 Ciliary body (3)   2.10 Lens (0)   2.11 Vitreous body (0)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (2)   2.13 Retina and retinal nerve fibre layer (20)   2.14 Optic disc (18)   2.15 Optic nerve (2)   2.16 Chiasma and retrochiasmal central nervous system (1)   2.17 Stem cells (0)   2.20 Other (0) 3 Laboratory methods (2)   3.1 Microscopy (3)   3.2 Electron microscopy (2)   3.3 Immunohistochemistry (8)   3.4 Molecular genetics (2)     3.4.1 Linkage studies (8)     3.4.2 Gene studies (3)   3.5 Molecular biology incl. SiRNA (9)   3.6 Cellular biology (6)   3.7 Biochemistry (3)   3.8 Pharmacology (5)   3.9 Pathophysiology (2)   3.10 Immunobiology (0)   3.11 Pharmacogenetics (0)   3.12 Proteomics (0)   3.13 In vivo imaging (0)     3.13.1 Laser Scanning (0)       3.13.1.1 Confocal Scanning Laser Ophthalmoscopy (0)       3.13.1.2 Confocal Scanning Laser Polarimetry (0)     3.13.2 Optical Coherence Tomography (0)       3.13.2.1 Anterior Segment (0)       3.13.2.2 Posterior Segment (0)     3.13.3 RGC Imaging (0)     3.13.4 Other (0)   3.20 Other (0) 4 Tissue culture of ocular cells (0) 5 Experimental glaucoma; animal models (20)   5.1 Rodent (0)   5.2 Primates (0)   5.3 Other (0) 6 Clinical examination methods (0)   6.1 Intraocular pressure measurement; factors affecting IOP (11)     6.1.1 Devices, techniques (0)     6.1.2 Fluctuation, circadian rhythms (0)     6.1.3 Factors affecting IOP (0)   6.2 Tonography, aqueous flow measurement (see also 2.6) (1)   6.3 Biomicroscopy (slitlamp) (0)     6.3.1 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Refractive errors in relation to glaucoma (0)   8.1 Myopia (0)   8.2 Hypermetropia (0)   8.3 Contact lenses (1)   8.4 Refractive surgical procedures (0)   8.5 Other (0) 9 Clinical forms of glaucomas (0)   9.1 Developmental glaucomas (3)     9.1.1 Congenital glaucoma, Buphthalmos (0)     9.1.2 Juvenile glaucoma (0)     9.1.3 Syndromes of Axenfeld, Rieger, Peters, aniridia (4)     9.1.4 Other (0)   9.2 Primary open angle glaucomas (0)     9.2.1 Ocular hypertension (0)     9.2.2 Other risk factors for glaucoma (8)     9.2.3 Open angle glaucoma with elevated IOP (1)     9.2.4 Normal pressure glaucoma (6)   9.3 Primary angle closure glaucomas (1)     9.3.1 Acute primary angle closure glaucoma (pupillary block) (2)     9.3.2 Chronic primary angle closure glaucoma (pupillary block) (2)     9.3.3 Plateau iris syndrome (1)     9.3.4 Primary angle closure suspect (0)     9.3.5 Primary angle closure (0)     9.3.10 Other (1)   9.4 Glaucomas associated with other ocular and systemic disorders (0)     9.4.1 Steroid-induced glaucoma (0)     9.4.2 Glaucomas associated with disorders of the cornea, conjunctiva, sclera (0)       9.4.2.1 Iridocorneal endothelial syndrome (ICE, incl. irisatrophy) (0)       9.4.2.2 Posterior polymorphous dystrophy (0)       9.4.2.3 Fuchs' endothelial dystrophy (0)       9.4.2.5 Other (0)     9.4.3 Glaucomas associated with disorders of the iris and ciliary body (1)       9.4.3.1 Pigmentary glaucoma (6)       9.4.3.5 Other (0)     9.4.4 Glaucomas associated with disorders of the lens (0)       9.4.4.1 Exfoliation syndrome (2)       9.4.4.2 Glaucomas associated with cataracts (1)       9.4.4.3 Glaucomas associated with lens dislocation (0)       9.4.4.5 Other (0)     9.4.5 Glaucomas associated with disorders of the retina, choroid and vitreous (0)       9.4.5.1 Neovascular glaucoma (2)       9.4.5.5 Other (0)     9.4.6 Glaucomas associated with inflammation, uveitis (0)     9.4.7 Glaucomas associated with ocular trauma (0)     9.4.8 Glaucomas associated with intraocular tumors (0)     9.4.9 Glaucomas associated with elevated episcleral venous pressure (1)       9.4.10 Glaucomas associated with hemorrhage (0)     9.4.11 Glaucomas following intraocular surgery (0)       9.4.11.1 Ciliary block (malignant) glaucoma (0)       9.4.11.2 Glaucomas in aphakia and pseudophakia (1)       9.4.11.3 Epithelial, fibrous, and endothelial proliferation (0)       9.4.11.4 Glaucomas associated with corneal surgery (3)       9.4.11.5 Glaucomas associated with vitreoretinal surgery (0)     9.4.15 Glaucoma in relation to systemic disease (4)     9.4.20 Other (0) 10 Differential diagnosis e.g. anterior and posterior ischemic optic neuropathy (4) 11 Medical treatment (0)   11.1 General management, indication (8)   11.2 Cholinergic drugs (4)   11.3 Adrenergic drugs (0)     11.3.1 Epinephrine (0)     11.3.2 Thymoxamine, dapiprazole (0)     11.3.3 Apraclonidine, brimonidine (4)     11.3.4 Betablocker (12)     11.3.5 Other (1)   11.4 Prostaglandins (31)   11.5 Carbonic anhydrase inhibitors (0)     11.5.1 Systemic (0)     11.5.2 Topical (7)   11.6 Osmotic treatment (1)   11.7 Treatment of bloodflow (1)   11.8 Neuroprotection (7)   11.9 Gene therapy (2)   11.13 Combination therapy (0)     11.13.1 Betablocker and pilocarpine (0)     11.13.2 Betablocker and carbon anhydrase inhibitor (0)     11.13.3 Betablocker and brimonidine (0)     11.13.4 Betablocker and prostaglandin (0)     11.13.5 Other (0)   11.14 Investigational drugs; pharmacological experiments (7)   11.15 Other drugs in relation to glaucoma (0)   11.16 Vehicles, delivery systems, pharmacokinetics, formulation (1)   11.17 Cooperation with medical therapy e.g. persistency, compliance, adherence (0)   11.20 Other (0) 12 Surgical treatment (0)   12.1 General management, indication (5)   12.2 Laser iridotomy (0)   12.3 Laser iridoplasty (0)   12.4 Laser trabeculoplasty and other laser treatment of the angle (1)   12.7 Surgical iridectomy (0)   12.8 Filtering surgery (1)     12.8.1 Without tube implant (4)     12.8.2 With tube implant or other drainage devices (11)     12.8.3 Non-perforating (13)     12.8.4 Using laser (0)     12.8.5 Other (0)     12.8.10 Woundhealing antifibrosis (10)     12.8.11 Complications, endophthalmitis (6)   12.9 Trabeculotomy, goniotomy (1)   12.10 Cyclodestruction (3)   12.11 Cyclodialysis (0)   12.12 Cataract extraction (0)     12.12.1 Intracapsular (0)     12.12.2 Extracapsular (1)     12.12.3 Phacoemulsification (2)   12.14 Combined cataract extraction and glaucoma surgery (0)     12.14.1 Intracapsular (0)     12.14.2 Extracapsular (0)     12.14.3 Phacoemulsification (6)   12.15 Capsulotomy (0)   12.16 Vitrectomy (0)   12.17 Anesthesia (0)   12.20 Other (2) 13 Therapeutic prognosis and outcome (0)   13.1 Prognostic factors (0)   13.2 Outcome (0)     13.2.1 IOP (0)     13.2.2 Visual field (0)       13.2.2.1 Progression (0)       13.2.2.2 Improvement (0)     13.2.3 Other (0) 14 Costing studies; pharmacoeconomics (5) 15 Miscellaneous (2)

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Abstract #8982 Published in IGR 5-2

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

Hellberg MR; Ke TL; Haggard K; Klimko PG; Dean TR; Graff G
Journal of Ocular Pharmacology and Therapeutics 2003; 19: 97-103

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Bimatoprost (Lumigan), the ethyl amide derivative of the potent prostaglandin FP agonist 17-phenyl-trinor PGF_2ALP, 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 analogue prodrug, the hydrolysis of bimatoprost by ocular tissues was studied by incubating solutions containing bimatoprost with either human or rabbit ocular tissue. The ethyl amide group of bimatoprost was hydrolyzed by rabbit and human cornea, iris/ciliary body and Thasclera to produce the expected carboxylic acid product, 17-phenyl-trinor PGF_2ALP. The rate of hydrolysis by human and rabbit cornea and iris/ciliary body is similar, whereas the rate of hydrolysis by the sclera is slower in humans than in rabbits. These studies show that human and rabbit ocular tissue (cornea, iris/ciliary body and sclera) can convert bimatoprost to the potent prostaglandin FP agonist 17-phenyl-trinor PGF_2ALP. Separate in vitro studies clearly show that both bimatoprost and 17-phenyl-trinor PGF_2ALP have affinity for and are agonists at the human FP receptor. Taken together, the data strongly suggest that the ocular hypotensive effect of bimatoprost can be attributed to its activity as a prostaglandin receptor agonist either directly or through its role as a prostaglandin agonist prodrug.

Dr. M.R. Hellberg, Alcon Research Ltd., Fort Worth, TX 76134, USA. mark.hellberg@alconlabs.com

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Classification:

11.4 Prostaglandins (Part of: 11 Medical treatment)

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