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A synthetic glucocorticoid and derivative of fluocinolone acetonide with anti-inflammatory and antipruritic activities. Fluocinonide binds the glucocorticoid receptor, followed by translocation of the ligand-receptor complex to the nucleus and transcription activation of genes containing glucocorticoid-responsive elements. Lipocortin-1 is one factor induced by fluocinonide that interacts and inhibits cytosolic phospholipase 2 alpha, thereby preventing phospholipase translocation to the perinuclear membrane and subsequent release and conversion of arachidonic acid to inflammatory prostaglandins. In addition, MAPK phosphatase 1 is induced, thereby preventing the triggering of the MAPK cascade resulting in pro-inflammatory effects via Jun N-terminal kinase and c-Jun. Finally, fluocinonide binds to and inhibits nuclear factor kappa-B directly, resulting in inhibition of cyclooxygenase 2 transcription and subsequent prostaglandin synthesis.
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