The
histamine receptor H1 antagonist
homochlorcyclizine (HC) has been widely used as an
antihistamine agent for the treatment of
allergies. However, the effect of HC on skin pigmentation is not known. In the present study, we investigated the inhibitory effect of HC on melanogenesis in mouse
B16 melanoma cells. Our results showed that HC inhibited melanogenesis in either α-
melanocyte stimulating hormone (α-
MSH)- or 3-isobutyl-1-methylxanthin (
IBMX)-stimulated B16 cells in a dose-dependent manner. Despite the strong inhibition of melanogenesis by HC, it was surprisingly found that HC did not reduce either cellular or melanosomal
tyrosinase activity in α-
MSH-stimulated B16 cells. In addition, HC also did not directly inhibit either murine or mushroom
tyrosinase activity in the cell-free system. Moreover, western blotting and reverse-transcription polymerase chain reaction (RT-PCR) analyses respectively confirmed that HC did not downregulate levels of
tyrosinase protein and its
mRNA in α-
MSH-stimulated B16 cells. These results clearly demonstrated that HC inhibits melanogenesis of B16 cells by a mechanism other than reduction of the cellular
tyrosinase activity. From the present study, HC was proven to be a good candidate as a
skin-whitening agent for treatment of skin
hyperpigmentation, and this
generic drug might be suitable for use in combination with other
depigmenting agents due to its unique inhibition mechanism.