1998 - SK&F 106615
Inflamm Res. 1998 Feb;47(2):56-61. Related Articles, Links
Evaluation of the cutaneous anti-inflammatory activity of azaspiranes.
Griswold DE, Martin LD, Badger AM, Breton J, Chabot-Fletcher M.
Department of Immunopharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA. Don_E_Griswold@SBPHRD.com
OBJECTIVE AND DESIGN:
The ability of azaspiranes to modulate the acute inflammatory response in models of skin inflammation was examined.
MATERIAL:
The in vivo experiments involved the use of 5-6 age-matched male Balb/c inbred mice (22-25 g) per treatment group and a control group of 8-10 animals. In vitro mechanistic studies used RBL-1 and U937 cells lines and freshly isolated human monocytes.
TREATMENT:
Arachidonic acid (AA) (2 mg/20 microl in acetone) or PMA (phorbol myristate acetate) (4 microg/20 microl) were applied topically. SK&F 106615 and SK&F 106610 were administered topically either dissolved in acetone or dimethylacetamide just after the application of the irritant.
Isolated cells were treated with the compounds dissolved in DMSO.
METHODS:
The thickness and influx of neutrophils into the treated ears was measured as was the effects of the azaspiranes on 5-lipoxygenase activity, cyclooxygenase activity, prostaglandin and leukotriene synthesis, and the activation of the transcription factor NF-kappaB.
RESULTS:
SK&F 106615 and SK&F 106610 significantly reduced inflammation in the AA- and PMA-induced inflammation models (p < 0.05) with ED50's of 179 and 120 mg/ear for edema and myeloperoxidase, respectively.
The compounds did not inhibit eicosanoid biosynthesis, have a direct effect on 5-lipoxygenase or cyclooxygenase enzymes, or inhibit NF-kappaB.
CONCLUSIONS:
The potent anti-inflammatory and immunomodulatory activities of the azaspiranes observed in these and other studies appear to be mediated by a novel mechanism.
PMID: 9535542 [PubMed - indexed for MEDLINE]
ncbi.nlm.nih.gov |
