Effects of the New Ethacrynic Acid Derivative SA9000 on Intraocular Pressure in Cats and Monkeys
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- Shimazaki Atsushi
- Research and Development Center, Santen Pharmaceutical Co. Ltd.
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- Ichikawa Masaki
- Research and Development Center, Santen Pharmaceutical Co. Ltd.
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- Rao Ponugoti Vasantha
- Department of Ophthalmology, Duke University Medical Center & Health System
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- Kirihara Tomoko
- 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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- Epstein David Lee
- Department of Ophthalmology, Duke University Medical Center & Health System
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- Hara Hideaki
- Research and Development Center, Santen Pharmaceutical Co. Ltd.
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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) 3.8 mmHg in cats. A 10 μl intracameral injection of 1 mM SA9000 significantly reduced IOP 7 mmHg 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.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 27 (7), 1019-1024, 2004
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204627111808
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- NII論文ID
- 110003608906
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 6986631
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- PubMed
- 15256733
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
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- 使用不可