Retinoids - Which dermatological indications will benefit in the near future?

Retinoids are compounds with pleiotropic functions and a relatively selecti ve targeting of certain skin structures. They are vitamins, because retinol (vitamin A) is not synthesized in the body and must be derived from diet, but also hormones with intracrine activity, because retinol is transformed into molecules that bind to nuclear receptors, exhibit their activity, and are subsequently inactivated. Retinoids exert their effects on target cells by binding and activating nuclear retinoid receptors. Retinoid receptors b ind their ligands in form of dimers. Heterodimers can be formed between two different retinoid receptor molecules but also between retinoid X receptor s and the vitamin D receptor as well as the triiodothyronin receptor. This fact indicates complex interactions between retinoids and further hormonal signal transduction molecules. Interaction of retinoid receptors with trans criptional factors activated by other signal transduction mechanisms, e.g. AP-1, may provide dissociation of the retinoid effects. Retinoids can exhib it agonistic activity but also be neutral antagonists and inverse agonists. Topical and oral retinol, tretinoin, isotretinoin, and bexarotene, topical alitretinoin, retinaldehyde, motretinide, adapalene, tazarotene, and syste min acitretin compose the list of launched retinoids. Psoriasis and related disorders, congenital disorders of keratinization, acne, photoaging and hy povitaminosis A are classical approved indications of retinoid treatment, w hereas cutaneous T-cell lymphoma, AIDS-associated Kaposi's sarcoma, acute p romyelocytic leukemia and actinic lentigines were currently confirmed. In a ddition, retinoids have been successfully used in several other dermatoses, e.g. epithelial precanceroses and tumors, seborrhea, rosacea and acneiform dermatoses, lichen planus, eosinophilic folliculitis, condylomata accumina ta, lichen sclerosus and atrophicus. Highly receptor selective molecules, r etinoic acid receptor-beta -inducers, AP-1 complex antagonists, and inverse agonists will be probably lead the retinoid development in the near future . New, more effective and less toxic retinoids, alone or in combination wit h other drugs and new delivery systems may provide therapeutic solutions fo r benign and malignant proliferative skin diseases, such as psoriasis and n onmelanoma tumors, cancer chemoprevention and differentiation therapy. Copy right ((C)) 2001 S. Karger AG,Basel.