Linked Life Data

17666801

Source:http://linkedlifedata.com/resource/pubmed/id/17666801

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-8-1
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0918-6158
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1445-9
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Effects of the new ethacrynic acid oxime derivative SA12590 on intraocular pressure in cats and monkeys.
pubmed:affiliation
Research and Development Center, Santen Pharmaceutical Co. Ltd., 8916-16 Takayama, Ikoma 630-0101, Japan. atsushi.shimazaki@santen.co.jp
pubmed:publicationType
Journal Article