A Novel Nitric Oxide Releasing Prostaglandin Analog, NCX 125, Reduces Intraocular Pressure in Rabbit, Dog, and Primate Models of Glaucoma
| العنوان: | A Novel Nitric Oxide Releasing Prostaglandin Analog, NCX 125, Reduces Intraocular Pressure in Rabbit, Dog, and Primate Models of Glaucoma |
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| المؤلفون: | Minerva R. Batugo, Valerio Chiroli, Ganesh Prasanna, Valentina Borghi, Elena Bastia, Ennio Ongini, Liu Jia, Achim Hans-Peter Krauss, Francesco Impagnatiello, David J. Kucera, Massimiliano Guzzetta, Carol B. Toris, David Gale, Wesley K. M. Chong, Samantha Carreiro |
| المصدر: | Journal of Ocular Pharmacology and Therapeutics. 26:125-132 |
| بيانات النشر: | Mary Ann Liebert Inc, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Male, Intraocular pressure, medicine.medical_specialty, genetic structures, Iris, Nitric Oxide Synthase Type II, Glaucoma, Ocular hypertension, Prostaglandin, Pharmacology, Nitric Oxide, Nitric oxide, Aqueous Humor, chemistry.chemical_compound, Dogs, Prostaglandins, Synthetic, Tumor Cells, Cultured, Animals, Medicine, Pharmacology (medical), Latanoprost, Cyclic GMP, Antihypertensive Agents, Intraocular Pressure, Lagomorpha, biology, business.industry, Macrophages, Ciliary Body, medicine.disease, biology.organism_classification, eye diseases, Surgery, Disease Models, Animal, Macaca fascicularis, Ophthalmology, Prostaglandin analog, chemistry, Prostaglandins F, Synthetic, Female, Ocular Hypertension, Rabbits, sense organs, Ophthalmic Solutions, business |
| الوصف: | Nitric oxide (NO) is involved in a variety of physiological processes including ocular aqueous humor dynamics by targeting mechanisms that are complementary to those of prostaglandins. Here, we have characterized a newly synthesized compound, NCX 125, comprising latanoprost acid and NO-donating moieties.NCX 125 was synthesized and tested in vitro for its ability to release functionally active NO and then compared with core latanoprost for its intraocular pressure (IOP)-lowering effects in rabbit, dog, and nonhuman primate models of glaucoma.NCX 125 elicited cGMP formation (EC(50) = 3.8 + or - 1.0 microM) in PC12 cells and exerted NO-dependent iNOS inhibition (IC(50) = 55 + or - 11 microM) in RAW 264.7 macrophages. NCX 125 lowered IOP to a greater extent compared with equimolar latanoprost in: (a) rabbit model of transient ocular hypertension (0.030% latanoprost, not effective; 0.039% NCX 125, Delta(max) = -10.6 + or - 2.3 mm Hg), (b) ocular hypertensive glaucomatous dogs (0.030% latanoprost, Delta(max)= -6.7 + or - 1.2 mm Hg; 0.039% NCX 125, Delta(max) = -9.1 + or - 3.1 mm Hg), and (c) laser-induced ocular hypertensive non-human primates (0.10% latanoprost, Delta(max) = -11.9 + or - 3.7 mm Hg, 0.13% NCX 125, Delta(max) = -16.7 + or - 2.2 mm Hg). In pharmacokinetic studies, NCX 125 and latanoprost resulted in similar latanoprost-free acid exposure in anterior segment ocular tissues.NCX 125, a compound targeting 2 different mechanisms, is endowed with potent ocular hypotensive effects. This may lead to potential new perspectives in the treatment of patients at risk of glaucoma. |
| تدمد: | 1557-7732 1080-7683 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbb206a9e50a5682f368070807694c6a https://doi.org/10.1089/jop.2009.0120 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....cbb206a9e50a5682f368070807694c6a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15577732 10807683 |
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