Effects of the New Ethacrynic Acid Derivative SA9000 on Intraocular Pressure in Cats and Monkeys(Pharmacology)
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概要
- 論文の詳細を見る
To evaluate the pharmacological characteristics of the new ethacrynic acid (ECA) derivative SA9000, we examined its ocular hypotensive effects in cats and cynomolgus monkeys, its corneal toxicity in rabbits, and its binding affinities for forty-three receptors, ion channels, and second messenger systems. A 20 μl injection into the anterior chamber of eye (intracameral injection) of 0.1 mM SA9000 significantly reduced intraocular pressure (IOP) 3.8mmHg in cats. A 10μl intracameral injection of 1 mM SA9000 significantly reduced IOP 7mmHg in living monkeys without evidence of in vivo (or in vitro) toxicity. The ocular hypotensive effect of SA9000 in monkeys was greater than that of ECA. The morphology of corneal endothelial and epithelial cells in rabbit eyes after intracameral injection of SA9000 was observed using electron microphotography. SA9000 at 2 mM did not induce any abnormalities, indicating that it has no corneal toxicity at a concentration higher than the minimum needed for an ocular hypotensive effect (1 mM). SA9000 at 0.01 mM showed negligible binding affinity for, or inhibition of, forty-three different receptors, ion channel proteins, and second messenger systems. These findings indicate that SA9000 has the potential to be both effective and safe as an ocular hypotensive drug, although the mechanism of action remains unclear.
- 公益社団法人日本薬学会の論文
- 2004-07-01
著者
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Epstein David
Department Of Ophthalmology Duke University Medical Center & Health System
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Epstein David
参天製薬奈良研究開発センター
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Ichikawa M
Healthcare Research Institute Wakunaga Pharmaceutical Co. Ltd.
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Hara Hideaki
Research And Development Center Santen Pharmaceutical Co. Ltd.
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SHIMAZAKI Atsushi
Research and Development Center, Santen Pharmaceutical Co., Ltd.
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KIRIHARA Tomoko
Research and Development Center, Santen Pharmaceutical Co., Ltd.
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RAO Ponugoti
Department of Ophthalmology, Duke University Medical Center & Health System
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ICHIKAWA Masaki
Research and Development Center, Santen Pharmaceutical Co., Ltd.
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KONOMI Kouji
Research and Development Center, Santen Pharmaceutical Co. Ltd.
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KONOMI Koji
Research and Development Center, Santen Pharmaceutical Co. Ltd.
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Kirihara Tomoko
Research And Development Center Santen Pharmaceutical Co. Ltd.
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Rao Ponugoti
Department Of Ophthalmology Duke University Medical Center & Health System
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Konomi Koji
Research And Development Center Santen Pharmaceutical Co. Ltd.
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Shimazaki Atsushi
Research And Development Center Santen Pharmaceutical Co. Ltd.
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Hara H
(present Address)corporate Planning Dept. Yamanouchi Pharmaceutical Co. Ltd.
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Ichikawa Masaki
Research And Development Center Santen Pharmaceutical Co. Ltd.
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