cyclic-gmp and Erythema

Anthralin was first synthesized in 1916. Earlier, a natural product, chrysarobin, originally derived from the South American araroba tree, had been used to treat psoriasis. Anthralin was first used in Germany, and later in the Ingram regimen in Britain, but it has never been popular with American dermatologists. This is probably due to the side effects of staining and irritation of the skin. Attempts to reduce these using low concentration, short contact therapy, and concomitant steroid therapy, have been only partially successful. It may be that better instruction of patients and physicians will lead to wider use of this effective topical agent for the treatment of psoriasis. The mode of action of anthralin is thought to be either through its effect on deoxyribonucleic acid (DNA), probably mitochondrial DNA, which reduces cell turnover, or through its effects on various enzyme systems, including those of polyamine synthesis and respiration. The aims of this review are to discuss historical aspects of anthralin and to update its chemistry, pharmacology, and clinical usage.

Topics: Anthracenes; Anthralin; Cell Division; Chemistry; Cyclic AMP; Cyclic GMP; DNA Replication; Drug Administration Schedule; England; Erythema; Glucosephosphate Dehydrogenase; History, 19th Century; History, 20th Century; Humans; Mitochondria; Oxidation-Reduction; Polyamines; Psoriasis; Skin Absorption; Skin Neoplasms; Structure-Activity Relationship

Topics: Chemotactic Factors; Chemotaxis, Leukocyte; Cyclic AMP; Cyclic GMP; Dermatitis Herpetiformis; Erythema; Histamine Release; Humans; Immunoglobulin E; Muramidase; Neutrophils; Skin; Skin Diseases; Staphylococcal Infections

Daily treatment of guinea-pig ear skin with topical 0.5% retinoic acid in acetone produced erythematous scaly dermatitis. Histologic sections revealed bandlike thickening of the epidermis on days 2 to 4, psoriasiform acanthosis, papillomatosis and increased mitotic activity on days 5 to 6. Also seen were dilatation of the upper dermal blood vessels and a fibroblastic, histiocytic reaction in the dermis. Prostaglandin E, cyclic AMP, and cyclic GMP levels were increased in the treated skin and thymidine incorporation was enhanced. Cyclic AMP and GMP levels peaked on day 5 simultaneous with maximal epidermal hyperplasia, increased mitotic activity and dermal reaction. Tritiated thymidine uptake peaked on days 4 and 5, and prostaglandin E levels continued to increase up to day 6. Cyclic AMP phosphodiesterase activity of treated skin on day 5 did not appear to be significantly different from control.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Administration, Topical; Animals; Cell Division; Cyclic AMP; Cyclic GMP; Disease Models, Animal; Erythema; Guinea Pigs; Male; Models, Biological; Prostaglandins E; Psoriasis; Skin; Skin Physiological Phenomena; Thymidine; Tretinoin; Vitamin A