Adapalene, a New Chemical Entity with Retinoid Activity

Abstract

Adapalene is a novel chemical entity which, in terms of pharmacology, behaves similar to tretinoin, but is chemically and photochemically stable. It has a particular selectivity profile for the known nuclear retinoic acid receptors with low affinity for RARΑ and no transactivating potential for RXRΑ. This receptor profile could imply that adapalene, in contrast to tretinoin, affects the terminal differentiation pathway of epidermal cells rather than their proliferation. Furthermore, adapalene does not bind to members of the cellular retinoic acid binding protein family. Adapalene has comedolytic activity in the topical rhino mouse model. It exerts a moderate-to-potent anti-inflammatory effect in a series of in vitro and in vivo models. In comparative clinical studies involving 72 acne patients, the efficacy of adapalene was comparable, if not superior, to tretinoin, but adapalene was better tolerated. The data reviewed in this paper indicate that adapalene should be particularly beneficial in the treatment of acne.

Oral Azithromycin Pulse Therapy and Daily Topical Adapalene in the Treatment of Acne Vulgaris: An Open Randomized Noncomparative Study

“…At the end of 12 weeks treatment 87% improvement observed in term of percent reduction of MichaelssonAcne Severity Index. These findings are more superiortothose observed in different studies by using azithromycin 4,5,7 and topicaladapalene 3,1011,12,13 alone.…”

Topical tretinoin or adapalene in acne vulgaris: an overview

“…14 Furthermore, it induces CRABP II synthesis, resulting in the buffering of excessive free retinoic acid, while its lack of binding to CRABP itself prevents possible problems of intraepidermal storage. 3 …”

“…[1][2][3] Two main types of nuclear receptors have been characterized: retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Each receptor family includes three subtypes: alpha, beta, and gamma.…”

“…[4][5][6] It is associated with keratinocyte differentiation and is most significant in the pathogenesis of acne. 3 Cytosolic retinoic acid binding proteins (CRABP) modulate the concentration of intracellular active retinoic acid and influence retinoid transport to cell nuclei, but are not relevant to the control exerted by retinoids on the differentiation of cultured keratinocytes. 7-10 A few cell lines devoid of CRABP, however, respond to retinoids, 11 and certain synthetic retinoids, with no affinity for CRABP, may bind retinoic acid nuclear receptors, 12 although it remains unclear how such retinoids (adapalene) reach their cognate nuclear receptors.…”

Plantar warts treated with topical adapalene

“…Adapalene a naphthoic acid derivative with retinoid like activity is commonly used topically for the treatment of mild to moderate acne vulgaris. [1] It binds to sub-type Y retinoic acid receptors found predominantly in the epidermis[2] and modulate cellular differentiation. [3] It also exhibits anti-inflammatory and anti-keratinisation activity.…”