methyl-prednisolonate and methyl-20-dihydroprednisolonate

Clinically used topical anti-inflammatory adrenal steroids inhibit skin collagen synthesis. This impaired collagen synthesis may result in dermal atrophy. Structure activity studies contrasted the effects of the novel prednisolone derivatives, methylprednisolonate , and methyl 20 dihydroprednisolonate , with presently used anti-inflammatory adrenal steroids on granuloma formation and skin collagen synthesis. These two new prednisolone derivatives, when applied locally at equivalent-potency anti-inflammatory doses compared with other corticosteroids, markedly inhibit granuloma formation but do not inhibit skin collagen synthesis nor cause dermal atrophy in rats. The data indicate that the two prednisolone acid methyl esters may be safer topical anti-inflammatory adrenal steroids to use, since they do not inhibit normal skin collagen synthesis.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Atrophy; Collagen; Granuloma; Prednisolone; Rats; Rats, Inbred Strains; Skin; Triamcinolone

When two new steroids, methyl prednisolonate and methyl 20-dihydroprednisolonate, were applied locally their anti-inflammatory activities were nearly equivalent to those of the parent compound prednisolone in the cotton pellet granuloma bioassay. However, when these two derivatives were administered systemically, their anti-inflammatory activities were weaker than those of the parent compound. Furthermore, unlike the parent compound, these new anti-inflammatory steroids did not suppress pituitary-adrenal function or cause liver glycogen depletion in rats.

Topics: Administration, Topical; Adrenocorticotropic Hormone; Animals; Anti-Inflammatory Agents; Corticosterone; Liver Glycogen; Pituitary-Adrenal System; Prednisolone; Rats

Steroid acid esters, synthesized by modifying the 17-ketol side chain of prednisolone, were tested for their in vitro ability to stabilize heavy mitochondrial lysosomes prepared from rat liver. Membrane stabilization was determined by assessing capability of steroids to decrease extrusion of the marker enzymes (acid phosphatase, beta-glucuronidase and aryl sulfatase) from lysosomes incubated in hypo-osmotic sucrose-Tris acetate buffer. Results indicated that prednisolone (1) significantly inhibited the lysosomal release of acid phosphatase as did the new anti-inflammatory steroid, methyl 20-dihydroprednisolonate. Methyl prednisolonate exhibited weak membrane stabilization capacities and 20-dihydroprednisolonic acid, a metabolic product of methyl 20-dihydroprednisolonate, showed virtually no membrane stabilization.

Topics: Acid Phosphatase; Animals; Anti-Inflammatory Agents; Arylsulfatases; Glucuronidase; Liver; Lysosomes; Male; Prednisolone; Rats; Rats, Inbred Strains

The antiinflammatory activity of two new steroids synthesized by modifying the 17 beta-ketol side chain of prednisolone to the glycolate and glyoxylate methyl esters has been investigated in the carrageenin pedal edema test in rats. The two ester derivatives retained anti-inflammatory potency, nearly equivalent to that of the parent compound, when administered subcutaneously at the site of inflammation. However, the glyoxylate ester, when administered by systemic route, showed a weaker suppression of inflammation. The glycolate ester showed a reverse trend in that it was more effective when it was administered by systemic route than when it was applied topically.

Topics: Administration, Oral; Administration, Topical; Animals; Anti-Inflammatory Agents; Edema; Injections, Subcutaneous; Male; Prednisolone; Rats