Clinical Aspects of Topical Retinoids

Abstract

Topical retinoids have been employed in dermatology since the 1960s to treat a wide variety of cutaneous disorders. This review focuses on three areas in which retinoids have had their greatest impact: acne vulgaris, photoaging and cutaneous neo-plasia. The pharmacology of the available topical retinoids, their mechanism of action and the history of their use in these disorders are discussed.

Alpha‐hydroxyacids and carboxylic acids

“…Since differentiation is integral to keratinization, vitamin A has therapeutic values for the skin, and on a molar basis the effect on skin keratinization in decreasing order is retinoic acid, retinal and retinol. Vitamin A acid on topical application promotes proliferation and differentiation of epithelial cells, and stimulates synthesis of collagen I and III; it is therapeutically effective for topical treatment of acne, actinic keratoses and photoaged skin 51–55 . Two synthetic retinoids, tazarotene and adapalene, which do not have conventional vitamin A structure, have been found to be therapeutically effective for topical treatment of acne 12 .…”

“…Vitamin A acid on topical application promotes proliferation and differentiation of epithelial cells, and stimulates synthesis of collagen I and III; it is therapeutically effective for topical treatment of acne, actinic keratoses and photoaged skin. [51][52][53][54][55] Two synthetic retinoids, tazarotene and adapalene, which do not have conventional vitamin A structure, have been found to be therapeutically effective for topical treatment of acne. 12 The unwanted sideeffects of topical retinoids include dry skin, erythema, pruritus, burning and stinging.…”

Structure−Activity Relationship Studies of Novel Heteroretinoids: Induction of Apoptosis in the HL-60 Cell Line by a Novel Isoxazole-Containing Heteroretinoid

“…14 Thus, as a result of the multiplicity of receptors, hormones, and dimerization pathways, it is likely that the many biological effects associated with retinoids are in fact mediated by several distinct pathways. However, the wider use of retinoids in dermatology (principally in the therapy of psoriasis and acne) 10,15,16 and in other diseases such as oncology (treatment of carcinomas and for cancer chemoprevention) 17,18 has been precluded by unacceptable side effects 19 including skin irritation, lipid and bone toxicity, visual effects, and teratogenicity. 7,19 To increase the selectivity to the retinoid receptors and to obtain compounds of pharmacological interest, the relationships between structure and retinoid activity have been extensively studied by preparing a large number of geometric isomers as well as conformationally locked and/or restricted analogues, resulting in specific, rigid, three-dimensional configurations.…”

“…Thus, as a result of the multiplicity of receptors, hormones, and dimerization pathways, it is likely that the many biological effects associated with retinoids are in fact mediated by several distinct pathways. However, the wider use of retinoids in dermatology (principally in the therapy of psoriasis and acne) ,, and in other diseases such as oncology (treatment of carcinomas and for cancer chemoprevention) , has been precluded by unacceptable side effects including skin irritation, lipid and bone toxicity, visual effects, and teratogenicity. , …”

Synthesis and Characterization of a Highly Potent and Selective Isotopically Labeled Retinoic Acid Receptor Ligand, ALRT1550

“…Retinoids are small organic molecules comprising vitamin A, its metabolites, and synthetic analogues. These compounds act as modulators of nuclear transcription by binding to and activating one or more of the six characterized intracellular retinoid receptors, retinoic acid receptors (RARα,β,γ), and retinoid X receptors (RXRα,β,γ). , This results in regulation of numerous cellular processes such as development, reproduction, bone formation, hematopoiesis, and immune function. , These biological actions also have implications for treatment of dermatological diseases and certain cancers. , Endogenous retinoids such as all - trans -retinoic acid (ATRA, 1a ) (Chart ), a RAR-selective agonist, and 9- cis -retinoic acid ( 1b , ALRT1057), a pan agonist (activates all six retinoid receptors − ), as well as a variety of synthetic retinoids including 13- cis -RA, etretinate, Tazarotene, and Targretin, have shown clinical utility, − for the treatment of acne, psoriasis, acute promyelocytic leukemia, squamous cell carcinoma, melanoma, and Kaposi's sarcoma. , The therapeutic effects of these compounds result from their ability to control abnormal cellular processes by modulating cellular differentiation, inhibiting cellular proliferation, and regulating apoptosis.

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