Mechanistic studies on the selective inhibition of cyclooxygenase-2 by indanone derivatives.

The cyclooxygenase step in the conversion of arachidonic acid is a key point in the biosynthesis of prostanoids, managed by two enzymatic isoforms. In the following study we focused on the mechanism of the inhibitory action of CGP 28238 and structurally-related indanone derivatives using purified enzymes. Consistent with our earlier studies on cell systems, CGP 28238 revealed selective inhibition of cyclooxygenase-2.

Dermatopharmacologic investigations of halobetasol propionate in comparison with clobetasol 17-propionate.

Both halobetasol propionate and clobetasol 17-propionate exerted very marked antiinflammatory, antiproliferative, and vasoconstrictive effects during evaluation in a range of dermatopharmacologic models. Halobetasol propionate was distinctly more potent than clobetasol 17-propionate in the ultraviolet-induced dermatitis inhibition assay in guinea pigs and in the rat model of oxazolone-induced late inflammatory reaction. Halobetasol propionate was slightly more potent than clobetasol 17-propionate in inhibiting croton oil-induced ear edema in rats and mice and in the mouse model of oxazolone-induced early inflammatory reaction.

Pharmacological properties of five diclofenac metabolites identified in human plasma.

Five metabolites of diclofenac sodium (Voltarol) have been identified in human plasma. All five metabolites were more than 50 times less potent than diclofenac in inhibiting PGE2 production in zymosan-stimulated mouse macrophages and LTC4 synthesis was not inhibited in these cells. Anti-inflammatory activity (adjuvant arthritis and carragheenan-induced paw oedema in rats) and analgesic activity (phenyl-p-benzoquinone writhing, mouse) of the metabolites were at least 10 times lower when compared to diclofenac.

The pharmacological profile of CGP 28238, a novel highly potent anti-inflammatory compound.

CGP 28238 (6-(2,4-difluorophenoxy)-5-methylsulfonylamino-1-indanone ) exhibits very potent anti-inflammatory activity in rat adjuvant arthritis (ED40 = 0.05 mg/kg, p.o.