Effects of the new ethacrynic acid oxime derivative SA12590 on intraocular pressure in cats and monkeys.

Journal Article (Journal Article)

To evaluate the pharmacological characteristics of SA12590, a new oxime-derivative of the ethacrynic acid (ECA) derivative SA9000, we examined both its ocular hypotensive effects (in ocular normotensive cats and cynomolgus monkeys) and its potential corneal toxicity (in rats). A 50 microl topical administration of 3% SA12590 significantly reduced intraocular pressure (IOP) (by 3.5 mmHg) in anesthetized cats (p<0.05). Twenty-four hours after 3 drops (5-min intervals) of 20 microl 3% SA12590, IOP was reduced by 8 mmHg (p<0.05, n=4) in conscious monkeys without evidence of corneal toxicity. Three days' daily single 20 microl dosing with 3% SA12590 reduced IOP by 4 mmHg (p<0.01, n=3) at 72 h after the first administration in conscious monkeys. The toxicity of topically administered 20 microl 3% SA9000 or SA12590 (3 drops with 5-min intervals) on rat corneal epithelium was assessed using a photo-slit lamp. In this study, 3% SA12590, unlike 3% SA9000, exhibited no corneal toxicity. In a glutathione assay for sulfhydryl (SH) reactivity, SA12590, unlike SA9000, displayed no in vitro SH reactivity. Thus, oxime-modification may both improve efficacy towards IOP upon topical administration and improve the safety profile, probably by enhancing corneal penetration and minimizing SH reactivity-related toxicity. These findings indicate that SA12590 has potential as a new ocular hypotensive drug.

Full Text

Duke Authors

Cited Authors

  • Shimazaki, A; Kirihara, T; Rao, PV; Tajima, H; Matsugi, T; Epstein, DL

Published Date

  • August 2007

Published In

Volume / Issue

  • 30 / 8

Start / End Page

  • 1445 - 1449

PubMed ID

  • 17666801

International Standard Serial Number (ISSN)

  • 0918-6158

Digital Object Identifier (DOI)

  • 10.1248/bpb.30.1445


  • eng

Conference Location

  • Japan