benzofurans and Dermatitis

Mapracorat is a nonsteroidal Selective Glucocorticoid Receptor Agonist (SEGRA) that is presumed to have a better therapeutic index compared to classical glucocorticoids.. To compare the efficacy and safety of mapracorat with classical glucocorticoids used for the treatment of allergic skin diseases in dogs.. Six laboratory beagles.. The effect of mapracorat on lipopolysaccharide-induced TNFα secretion from canine peripheral blood derived mononuclear cells (PBMC) was tested. In vivo, mapracorat was compared to triamcinolone acetonide using a skin inflammation model. Skin fold thickness was determined after daily administration of mapracorat and triamcinolone acetonide over 14 days.. These results demonstrate that mapracorat has comparable anti-inflammatory efficacy to classical steroidal glucocorticoids under these experimental settings and maintenance of skin fold thickness indicates a better safety profile compared to triamcinolone acetonide at equipotent concentrations. This profile further suggests that SEGRAs show promise in the management of inflammatory and pruritic skin diseases in dogs.

Topics: Administration, Topical; Animals; Benzofurans; Dermatitis; Dermatologic Agents; Dog Diseases; Dogs; Female; Male; Pentanols; Quinolines; Receptors, Glucocorticoid; Treatment Outcome; Triamcinolone Acetonide; Tumor Necrosis Factor-alpha

The biochemical and biological profile of a topical anti-inflammatory agent, 2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol (L-651,896 inhibited the 5-lipoxygenase of rat basophilic leukemia cells with an IC50 of 0.1 microM and leukotriene synthesis by human PMN and mouse macrophages with IC50 values of 0.4 and 0.1 microM respectively. L-651,896 also inhibited prostaglandin E2 synthesis by mouse peritoneal macrophages (IC50 = 1.1 microM). This compound inhibited ram seminal vesicle cyclooxygenase activity at considerably higher concentrations, and this effect was directly related to substrate concentration. When applied topically to the mouse ear, L-651,896 lowered elevated levels of leukotrienes associated with arachidonic acid-induced skin inflammation and delayed hypersensitivity induced by oxazolone. However, while L-651,896 inhibited the increased vascular permeability induced by arachidonic acid, it had no effect on the edema associated with the immune-based response to oxazolone in the same tissue. Thus, it is possible that leukotrienes may play a role in some but not all inflammatory responses.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Arachidonate Lipoxygenases; Benzofurans; Dermatitis; Dinoprostone; Humans; Hypersensitivity, Delayed; Leukemia, Experimental; Lipoxygenase Inhibitors; Macrophages; Neutrophils; Oxazolone; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; SRS-A