Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1995-9-5
|
| pubmed:abstractText |
Granulocyte infiltration is a prominent feature of human psoriasis. Psoriatic lesional skin contains abnormally high amounts of immunoreactive leukotriene B4 (LTB4), a potent granulocyte chemotaxin in vivo and in vitro. SC-53228 [(+)-(S)-7-(3-}2-(cyclopropylmethyl)-3-methoxy-4- [(methylamino)carbonyl]phenoxy}propoxy}-3,4-dihydro-8-propyl-2H-1- benzopyran-2-propanoic acid], a second-generation LTB4 receptor antagonist, was tested topically and orally in phorbol ester-induced dermal inflammation in three species. Skin inflammation was induced by topical application of phorbol-12-myristate-13-acetate-(PMA/TPA) and assessed by ear thickness, levels of the neutrophil marker enzyme myeloperoxidase (MPO) and histological examination. In mice, SC-53228 inhibited inflammation with a topical ED50 value of 200 +/- 18 micrograms. When applied to guinea pigs, SC-53228 (100 micrograms) inhibited the MPO increase by 86%, while 1000 micrograms abrogated inflammation in rhesus macaques with no plasma accumulation of the drug. A 1% gel formulation was also efficacious in guinea pig PMA-induced epidermal inflammation. Furthermore, single oral dose administration to mice was efficacious (ED50 < 2.5 mg/kg) as was multidose administration to rhesus macaques. PMA-induced skin inflammation possesses some of the attributes of human psoriasis and an agent such as SC-53228 may have utility in the medical management of this condition.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/7-(3-(2-(cyclopropylmethyl)-3-methox...,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/Benzopyrans,
http://linkedlifedata.com/resource/pubmed/chemical/Gels,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Leukotriene B4,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0360-3997
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
19
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
333-46
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:7628862-Administration, Cutaneous,
pubmed-meshheading:7628862-Administration, Oral,
pubmed-meshheading:7628862-Animals,
pubmed-meshheading:7628862-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:7628862-Benzamides,
pubmed-meshheading:7628862-Benzopyrans,
pubmed-meshheading:7628862-Disease Models, Animal,
pubmed-meshheading:7628862-Drug Eruptions,
pubmed-meshheading:7628862-Drug Evaluation, Preclinical,
pubmed-meshheading:7628862-Ear, External,
pubmed-meshheading:7628862-Edema,
pubmed-meshheading:7628862-Female,
pubmed-meshheading:7628862-Gels,
pubmed-meshheading:7628862-Guinea Pigs,
pubmed-meshheading:7628862-Humans,
pubmed-meshheading:7628862-Male,
pubmed-meshheading:7628862-Mice,
pubmed-meshheading:7628862-Peroxidase,
pubmed-meshheading:7628862-Psoriasis,
pubmed-meshheading:7628862-Receptors, Leukotriene B4,
pubmed-meshheading:7628862-Tetradecanoylphorbol Acetate
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Dermal inflammation in primates, mice, and guinea pigs: attenuation by second-generation leukotriene B4 receptor antagonist, SC-53228.
|
| pubmed:affiliation |
Department of Inflammatory Diseases Research, Searle Research and Development, Skokie, Illinois 60077, USA.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|