The mechanism by which<unk>  promotes hair growth is not fully understood.<unk>  is an adenosine 5'-triphosphate-sensitive potassium channel opener, causing hyperpolarization of cell membranes. Theoretically, by widening blood vessels and opening potassium channels, it allows more oxygen, blood, and nutrients to the follicles. Moreover,<unk>  contains a nitric oxide moiety and may act as a nitric oxide agonist. This may cause follicles in the telogen phase to shed, which are then replaced by thicker hairs in a new anagen phase.<unk>  is a prodrug that is converted by sulfation via the sulfotransferase enzyme SULT1A1 to its active form,<unk>  sulfate. The effect of<unk>  is mediated by adenosine, which triggers intracellular signal transduction via both adenosine A1 receptors and two sub-types of adenosine A2 receptors (A2A and A2B receptors).<unk>  acts as an activator of the Kir6/SUR2 channel upon selective binding to SUR2. The expression of SUR2B in dermal papilla cells might play a role in the production of adenosine.<unk>  induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupled sulfonylurea receptor on the plasma membrane of dermal papilla cells. A number of in vitro effects of<unk>  have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor, prostaglandin synthesis and leukotriene B4 expression.<unk>  causes a redistribution of cellular iron through its apparent capacity to bind this metal ion. By binding iron in a Fenton-reactive form, intracellular hydroxyl radical production would ensue, but hydroxyl would be immediately trapped and scavenged by the<unk>  to generate a nitroxyl radical. It is presumed that this nitroxyl radical will be capable of reduction by glutathione to reform<unk> . Such a process would cycle until the<unk>  is otherwise metabolized and would result in rapid glutathione depletion with glutathione disulphide formation and therefore with concomitant consumption of NADPH/ NADH and other reducing equivalents.<unk>  inhibited PHD by interfering with the normal function of ascorbate, a cofactor of the enzyme, leading to a stabilization of HIF-1α protein and a subsequent activation of HIF-1. In an in vivo angiogenesis assay, millimolar<unk>  increased blood vessel formation in a VEGF-dependent manner.<unk>  inhibition of PHD occurs via interrupting ascorbate binding to iron. The structural feature of positioning amines adjacent to nitric oxide may confer the ability of millimolar<unk>  to chelate iron, thereby inhibiting PHD.<unk>  is capable of tetrahydrobiopterin inhibition as a cofactor for nitric oxide synthase.<unk>  stimulates prostaglandin E2 production by activating COX-1 and prostaglandin endoperoxide synthase-1 but inhibits prostacyclin production. Additionally, expression of the prostaglandin E2 receptor, the most upregulated target gene in the β-catenin pathway of DP cells, was enhanced by<unk> , which may enable hair follicles to grow continuously and maintain the anagen phase. Due to anti-fibrotic activity of<unk>  inhibition of enzyme lysyl hydroxylase present in fibroblast may result in synthesis of a hydroxylysine-deficient collagen.<unk>  can also potentially stimulate elastogenesis in aortic smooth muscle cells, and in skin fibroblasts in a dose-dependent manner. In hypertensive rats,<unk>  increases elastin level in the mesenteric, abdominal, and renal arteries by a decrease in "elastase" enzyme activity in these tissues. In rats, potassium channel openers decrease calcium influx which inhibits elastin gene transcription through extracellular signal-regulated kinase ½ (ERK 1/2)-activator protein 1 signaling pathway. ERK 1/2 increases, through elastin gene transcription, adequately cross-linked elastic fiber content synthetized by smooth muscle cells, and decreases the number of cells in the aorta.<unk>  possesses alpha 2-adrenoceptor agonist activity, stimulates the peripheral sympathetic nervous system (SNS) by way of carotid and aortic baroreceptor reflexes.<unk>  administration also brings an increase in plasma renin activity, largely due to the aforementioned activation of the SNS. This activation of the renin-angiotensin axis further prompts increased biosynthesis of aldosterone; whereas plasma and urinary aldosterone levels are increased early in the course of treatment with<unk> , over time these values tend to normalize presumably because of accelerated metabolic clearance of aldosterone in association with hepatic vasodilation.<unk>  may be involved in the inhibition of serotonergic (5-HT2) receptors.<unk>  might increase blood-tumor barrier permeability in a time-dependent manner by down-regulating tight junction protein expression and this effect could be related to ROS/RhoA/PI3K/PKB signal pathway.<unk>  significantly increases ROS concentration when compared to untreated cells. In vitro<unk>  treatment resulted in a 0.22 fold change for 5α-R2 (p < 0.0001). This antiandrogenic effect of<unk> , shown by significant downregulation of 5α-R2 gene expression in HaCaT cells, may be one of its mechanisms of action in alopecia.<unk>  is less effective when the area of hair loss is large. In addition, its effectiveness has largely been demonstrated in younger men who have experienced hair loss for less than 5 years.<unk>  use is indicated for central (vertex) hair loss only. Two clinical studies are being conducted in the US for a medical device that may allow patients to determine if they are likely to benefit from<unk>  therapy.
Minoxidil
Sodium nitroprusside
Nebivolol
Isosorbide dinitrate
Balsalazide
Atenolol
Nadolol
Captopril