The Effect of the H-1152P, a Potent Rho-Associated Coiled Coil-Formed Protein Kinase Inhibitor, in Rabbit Normal and Ocular Hypertensive Eyes

Autor:	Kengo Sumi, Masahiro Nishio, Hiroyoshi Hidaka, Yukitaka Uji, Masahiko Sugimoto, Kengo Ikesugi, Takaki Fukunaga
Rok vydání:	2009
Předmět:	Intraocular pressure medicine.medical_specialty Time Factors genetic structures medicine.drug_class Administration Topical medicine.medical_treatment Ocular hypertension Cellular and Molecular Neuroscience 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Ophthalmology medicine Animals Protein kinase A Protein Kinase Inhibitors Saline Intraocular Pressure Coiled coil rho-Associated Kinases Dose-Response Relationship Drug business.industry Rabbit (nuclear engineering) Protein kinase inhibitor medicine.disease eye diseases Sensory Systems Surgery Ocular Hypertension Rabbits sense organs High intraocular pressure business Conjunctiva
Zdroj:	Current Eye Research. 34:282-286
ISSN:	1460-2202 0271-3683
DOI:	10.1080/02713680902783763
Popis:	We wanted to determine the intraocular pressure (IOP)-lowering effect of H-1152P by utilizing a rabbit ocular hypertension-glaucoma model and normal eyes. H-1152P is a potent, Rho-associated, coiled, coil-forming protein kinase (ROCK) inhibitor.IOPs were monitored by a pneumatonometer in New Zealand White rabbits that were given topically administered H-1152P or vehicle alone. Animals were divided into four groups followed by topical administration of 0.1, 1.0, 10, and 28 mM H-1152P. To study the IOP-lowering effects on an elevated IOP model, a rabbit ocular hypertension model was created by water loading. All studies were carried out by monitoring of IOPs on H-1152P-administered right eyes and phosphate-buffered saline (PBS)-administered left eyes.In normotensive IOP rabbits, topical administration of H-1152P significantly decreased IOPs by 46.1 +/- 5.0% at 1% (28 mM) solution. This effect was dose dependent, as the maximum reduction of IOPs were observed between 60 and 90 min after topical administration (3.6 +/- 0.9 mmHg, 5.4 +/- 0.7 mmHg, 6.8 +/- 0.7 mmHg, and 7.2 +/- 1.9 mmHg at 0.1, 1.0, 10, and 28 mM H-1152P). In addition, in the rabbit ocular hypertension model, the topical administration of H-1152P (28 mM) significantly lowered IOPs starting at 30 minutes and lasting up to 300 minutes after water loading. The maximum IOP reduction, however, was observed at 90 minutes after water loading (10.6 +/- 2.3 mmHg). No serious side effects were observedin ocular tissues except for some conjunctival congestion that shortly disappeared within 3 hours.Topical administration of H-1152P potently decreased rabbit normotensive IOPs in a dose-dependent manner, and the duration of the IOP lowering was also elongated in a dose-dependent manner. In addition, H-1152P has a potent IOP-lowering effect on an ocular hypertension model. These result suggested that H-1152P could be a candidate for the next generation of glaucoma therapy.
Databáze:	OpenAIRE
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