Effects of the new ethacrynic acid derivative SA9000 on intraocular pressure in cats and monkeys.
Journal Article (Journal Article)
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 microl 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 microl 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.
Full Text
Duke Authors
Cited Authors
- Shimazaki, A; Ichikawa, M; Rao, PV; Kirihara, T; Konomi, K; Epstein, DL; Hara, H
Published Date
- July 1, 2004
Published In
Volume / Issue
- 27 / 7
Start / End Page
- 1019 - 1024
PubMed ID
- 15256733
Pubmed Central ID
- 15256733
International Standard Serial Number (ISSN)
- 0918-6158
Digital Object Identifier (DOI)
- 10.1248/bpb.27.1019
Language
- eng
Conference Location
- Japan