Isotretinoin - Mechanism of Action

Mechanism of Action

Isotretinoin's exact mechanism of action is unknown but several studies have shown that isotretinoin induces apoptosis (cell death) in various cells in the body such as cells in meibomian glands, hypothalamic cells, hippocampus cells and important for treatment of acne, in sebaceous gland cells.

One study found that isotretinoin significantly changed the expression of hundreds of genes in skin after 8 weeks of therapy.

Isotretinoin is also one of several drugs discussed in a recent study examining epigenetic side effects (for example DNA methylation) of common pharmaceuticals that leads to silencing of genes.

One study suggests the drug amplifies production of neutrophil-gelatinase-associated lipocalin (NGAL) in the skin, which has been shown to reduce sebum production by inducing apoptosis in sebaceous gland cells, while exhibiting an antimicrobial effect on Propionibacterium acnes. The drug decreases the size and sebum output of the sebaceous glands. Isotretinoin's combined impact on several of acne's contributory factors distinguishes it from alternative remedies, such as antibiotics, and accounts for its greater efficacy in severe, nodulocystic cases.

The effect on sebum production can be temporary and remission of the disease can be "complete and prolonged."

Isotretinoin has been speculated to down-regulate the telomerase enzyme and hTERT, inhibiting "cellular immortalization and tumorigenesis."

Isotretinoin has also been proved, according to a 2007 study, to inhibit the action of the metalloprotease MMP-9 (gelatinase) in sebum, without any influence in the action of TIMP1 and TIMP2 (tissue inhibitors of metalloproteases). It is already known that metalloprotases play an important role in the pathogenesis of acne, thus the inhibition of their action by isotretinoin is an additional mechanism of action that contributes to the efficacy of Isotretinoin.