<unk>  agents work by reducing the presence of melanin pigment in the skin. To accomplish this, there are several possible mechanisms of action: *Inhibition of the activity of tyrosinase: The catalytic action of tyrosinase is inhibited by the<unk>  agent. *Inhibition of the expression or activation of tyrosinase: The antimelanogenic agent causes less tyrosinase to be generated or prevents tyrosinase from being activated to its functional form. *Scavenging of the intermediate products of melanin synthesis. *Preventing the transfer of melanosomes to keratinocytes. *Directly destroying existing melanin. *Destroying melanocytes. Inhibition of tyrosinase Upregulation of tyrosinase caused by tyrosinase inhibitors. Several<unk>  agents, including tyrosinase inhibitors, have been found to cause an increase in the expression of tyrosinase, which by itself would increase melanin synthesis. Microphthalmia-associated transcription factor (MITF) is the master transcription factor that controls the expression of TYR, TRP1 and TRP2, MART1, PMEL17, and many other important proteins involved in the function of melanocytes. Downregulation of MITF decreases melanogenesis and is a mechanism of action of some<unk>  agents. Various signaling pathways and genetic mutations influence the expression of MITF. MC1R receptor and cAMP The melanocortin 1 receptor (MC1R) is a transmembrane and G-protein coupled receptor expressed in melanocytes. MC1R is an important target for the regulation of melanogenesis. Agonism of MC1R increases the ratio of eumelanin to pheomelanin and increases the generation of melanin overall. The MC1R and cAMP signaling pathway starts with the activation of MC1R, which causes activation of adenylyl cyclase (AC), which produces cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA), which activates by protein phosphorylation cAMP response element-binding protein (CREB), which upregulates MITF, of which CREB is a transcription factor. Alpha-melanocyte stimulating hormone (α-MSH), beta-melanocyte stimulating hormone (β-MSH), and adrenocorticotropic hormone are endogenous agonists of MC1R. Agouti signaling protein (ASIP) appears to be the only endogenous antagonist of MC1R. Synthetic MC1R agonists have been designed, such as the peptides afamelanotide and melanotan II. Mutations of the MC1R gene correlate and are at least partially responsible for red hair, white skin, and an increased risk for skin cancer in some individuals. Transfer of melanosomes Within the skin, melanocytes are present in the basal layer of the epidermis; from these melanocytes originate dendrites that reach keratinocytes. Melanosomes along with the melanin they contain are transferred from melanocytes to keratinocytes when keratinocytes are low in the epidermis. Keratinocytes carry the melanosomes with them as they move towards the surface. Keratinocytes contribute to skin pigmentation by holding the melanin originated in melanocytes and inducing melanogenesis through chemical signals directed at melanocytes. The transfer of melanosomes to keratinocytes is a necessary condition for the visible pigmentation of the skin. Blocking this transfer is a mechanism of action of some<unk>  agents. The protease-activated receptor 2 (PAR2) is a transmembrane and G-protein coupled receptor expressed in keratinocytes and involved in melanocyte transfer. Antagonists of PAR2 inhibit the transfer of melanosomes and have<unk>  affects, while agonists of PAR2 have the opposite effect. Destroying melanocytes Some compounds are known to destroy melanocytes; this mechanism of action is often used to remove the remaining pigmentation in cases of vitiligo.
Skin whitening
Dark skin
Hypopigmentation
Erythema
Dryness 
Tooth discoloration
Hyperpigmentation
Oral pigmentation