Mechanism of action<unk> 's exact mechanism of action is unknown, but several studies have shown that<unk>  induces apoptosis (programmatic cell death) in various cells in the body. Cell death may be instigated in the meibomian glands, hypothalamic cells, hippocampus cells and—important for treatment of acne—in sebaceous gland cells.<unk>  has a low affinity for retinoic acid receptors (RAR) and retinoid X receptors (RXR), but may be converted intracellularly to metabolites that act as agonists of RAR and RXR nuclear receptors. 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 Cutibacterium acnes. The drug decreases the size and sebum output of the sebaceous glands.<unk>  is the only available acne drug that affects all four major pathogenic processes in acne, which distinguishes it from alternative treatments (such as antibiotics) and accounts for its efficacy in severe, nodulocystic cases. The effect of<unk>  on sebum production can be temporary, or remission of the disease can be "complete and prolonged."<unk>  has been speculated to down-regulate the enzyme telomerase and hTERT, inhibiting "cellular immortalization and tumorigenesis." In a 2007 study,<unk>  was proven to inhibit the action of the metalloprotease MMP-9 (gelatinase) in sebum without any influence in the action of TIMP1 and TIMP2 (the tissue inhibitors of metalloproteases). It is already known that metalloproteases play an important role in the pathogenesis of acne. CNS activities A possible biological basis for the case reports of depression involves decreased metabolism in the orbitofrontal cortex (OFC) of the frontal lobe. It has also been found that decreased OFC metabolism was correlated with headaches. People reporting headache as a side effect often report comorbid neuropsychiatric symptoms, especially depression; a statistically significant relationship between headache and depression has been established. It is suggested that people sensitive to<unk> -induced CNS effects may also be susceptible to other psychiatric side effects such as depression. Studies in mice and rats have found that retinoids, including<unk> , bind to dopaminergic receptors in the central nervous system.<unk>  may affect dopaminergic neurotransmission by disrupting the structure of dopamine receptors and decreasing dopaminergic activity. The dopaminergic system is implicated in numerous psychological disorders, including depression.<unk>  is also thought to affect the serotonergic system – it increases expression of 5-HT1A receptors in the pre-synaptic neuron, which inhibit serotonin secretion.<unk>  also directly and indirectly increases the translation of the serotonin transporter protein (SERT), leading to increased reuptake and consequently reduced synaptic availability of serotonin. Inhibition of hippocampal neurogenesis may also play a role in the development of<unk> -induced depression. A further effect of<unk>  on the brain involves retinoic acid function in the hypothalamus, the hormone regulatory centre of the brain and part of the hypothalamus-pituitary-adrenal axis, a key part of the body's stress response. Other brain regions regulated by retinoic acid and potentially disrupted by<unk>  include the frontal cortex and the striatum. Pharmacokinetics and pharmacodynamics Oral<unk>  is best absorbed when taken with a high-fat meal, because it has a high level of lipophilicity. The efficacy of<unk>  doubles when taken after a high-fat meal compared to when taken without food. Due to<unk> 's molecular relationship to Vitamin A, it should not be taken with Vitamin A supplements due to the danger of toxicity through cumulative overdosing. Accutane also negatively interacts with tetracycline, another class of acne drug, and with micro-dosed ('mini-pill') progesterone preparations, norethisterone/ethinylestradiol ('OrthoNovum 7/7/7'), St. John's Wort, phenytoin, and systemic corticosteroids.<unk>  is primarily (99.9%) bound to plasma proteins, mostly albumin. Three metabolites of<unk>  are detectable in human plasma after oral administration: 4-oxo-isotretinoin, retinoid acid (tretinoin), and 4-oxo-retinoic acid (4-oxo-tretinoin).<unk>  also oxidizes, irreversibly, to 4-oxo-isotretinoin—which forms its geometric isomer 4-oxo-tretinoin. After an orally-administered, 80 mg dose of liquid suspension 14C-isotretinoin, 14C-activity in blood declines with a half-life of 90 hours. The metabolites of<unk>  and its conjugates are then excreted in the subject's urine and faeces in relatively equal amounts. After a single, 80 mg oral dose of<unk>  to 74 healthy adult subjects under fed conditions, the mean ±SD elimination half-life (t1/2) of<unk>  and 4-oxo-isotretinoin were 21.0 ± 8.2 hours and 24.0 ± 5.3 hours, respectively. After both single and multiple doses, the observed accumulation ratios of<unk>  ranged from 0.90 to 5.43 in people with cystic acne.
Isotretinoin
Alitretinoin
Tretinoin
Clobetasol
Clobetasol propionate
Ulobetasol propionate
Ciclesonide
Tazarotene