A new synthetic
retinoid analogue,
adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-
naphthoic acid,
CD271), which is relatively selective for
retinoic acid receptor beta, was noted to be an effective comedolytic agent in the rhino mouse model and to have clinical efficacy against
acne. In pursuit of this observation, we studied the effects of
CD271 on the development of
erythema, spongiosis, and epidermal
hyperplasia as well as other well-characterized markers of in vivo
retinoid action after 4 d of occluded topical treatment. The objective of the study was to elucidate further those parameters associated with potential clinical efficacy. Twenty-five subjects were treated with 0.1%
all-trans retinoic acid cream,
all-trans retinoic acid vehicle, 0.1%
CD271 gel, or
CD271 vehicle under occlusion for 4 d. Only
all-trans retinoic acid induced
erythema (p < 0.01 versus all other treatments). Similarly, histologic analysis revealed that epidermal
hyperplasia and spongiosis were induced only by
all-trans retinoic acid (p < 0.01 versus all other treatments). By immunohistochemical analysis:
all-trans retinoic acid increased expression of epidermal
transglutaminase,
involucrin, and
calgranulin (p < 0.05 versus all other treatments). In contrast to these data, both
CD271 and
all-trans retinoic acid caused marked and significant (p < 0.05) elevation of
cellular retinoic acid-binding protein-II (
CRABP-II) messenger
ribonucleic acid steady-state levels as judged by quantitative
RNA blot analysis. Although
CD271 treatment did not lead to
erythema or affect epidermal morphology, its ability to induce a marker of
retinoid action (i.e.,
CRABP-II) was 70% the potency of
all-trans retinoic acid. This study suggests that
CRABP-II gene expression may be a more sensitive
indicator of
retinoid biologic activity in skin than are
erythema or changes in epidermal morphology and differentiation.