Chemistry:Minoxidil

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Minoxidil, sold under the brand names Loniten and Rogaine among others, is a medication used for the treatment of high blood pressure and hair loss.[1][2][3][4] It may also be used off-label to promote beard growth[5][6] and treat nail problems.[7][8] The drug promotes hair growth, but its effects are fully reversible and it does not slow or prevent hair loss.[4] It is available as a generic medication by prescription in oral tablet form and over-the-counter as a topical liquid or foam.[9][10][11][12] Oral minoxidil is used at high doses to treat high blood pressure and at low doses to treat hair loss, while topical minoxidil is used exclusively for hair loss and related indications.[13][14] Extended-release oral minoxidil[15][16][17] and sublingual minoxidil formulations for hair loss are also being studied and developed.[18][19]

Side effects of oral minoxidil may include low blood pressure, water retention and edema, salt retention, rapid heartbeat, dizziness, lightheadedness, headaches, excessive hair growth, and temporary hair shedding, among others.[13][14][20] Adverse effects of topical minoxidil include skin irritation, itching, dandruff, and temporary hair shedding, among others.[21] Rare but serious adverse effects of oral minoxidil include pericardial effusion, pleural effusion, cardiac tamponade, other cardiovascular complications, and pseudoacromegaly, among others.[13][22][23][24] Minoxidil is a prodrug of minoxidil sulfate, which acts as a KATP potassium channel opener to widen blood vessels and increase hair growth.[19][14][25][26][27] The effects of minoxidil are dose-dependently similar to the symptoms of Cantú syndrome.[14][25][26]

Minoxidil was discovered in 1963 and was introduced for treatment of high blood pressure in 1979.[28][29] It was unexpectedly found to cause hair growth in 1971, resulting in it being repurposed for treatment of hair loss and approved in topical form for this use in 1988.[28] Topical minoxidil became available over-the-counter in 1996.[28] Low-dose oral minoxidil (LDOM) emerged for treatment of hair loss in 2015[30][31] and dramatically increased in popularity starting in 2022.[14][22][32][30] Extended-release oral minoxidil and sublingual minoxidil were developed in the 2020s for hair loss and are in late-stage trials.[19][15][18] Aside from its use in humans, minoxidil is extremely toxic to cats and dogs even in small amounts.[33][34]

Medical uses

High blood pressure

Minoxidil, when used for hypertension, is generally reserved for use in severe hypertension patients who do not respond to at least two agents and a diuretic.[35] Minoxidil is also generally administered with a loop diuretic to prevent sodium retention and potassium retention.[35] It may also cause a reflex tachycardia and thus is prescribed with a beta blocker.[35]

Hair loss

Minoxidil is used for the treatment of hair loss.[4][36][37] It is mainly used topically, but in more recent years, it also being used at low doses orally and to a lesser extent sublingually.[4][19][36] The drug is effective in helping promote hair growth in both men and women with androgenic alopecia (androgen-dependent pattern hair loss).[37] It works by increasing hair counts as well as by thickening individual hair follicles.[4][19][38] Minoxidil 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. Minoxidil use is indicated for central (vertex) hair loss only.[39]

Minoxidil must be used indefinitely for continued support of existing hair follicles and the maintenance of any experienced hair regrowth.[2][3] Its benefits are tangible but fully reversible, with discontinuation following long-term treatment resulting in rapid hair loss and similar hair density as placebo at 24 weeks post-discontinuation.[4] As such, minoxidil does not appear to slow or prevent hair loss.[4]

Low-dose oral minoxidil (LDOM) is used off-label against hair loss and to promote hair regrowth.[30] Oral minoxidil is an effective and well-tolerated treatment alternative for patients having difficulty with topical formulations.[40][41][42] It is notable in this regard that topical minoxidil for hair loss has very low compliance rates, with almost all users discontinuing it after 1 year of use.[43][44] Consensus statements provide guidance on use of low-dose oral minoxidil for hair loss.[23][45][36] Dosing of low-dose oral minoxidil for hair loss has additionally been reviewed.[46][47][23] Higher doses are more effective for improving hair loss than lower doses, but also come with greater hypertrichosis incidence.[46]

Another option for hair loss treatment is sublingual minoxidil (SLM), which may have improved tolerability with retained efficacy compared to oral minoxidil.[19][48][38]

Minoxidil requires at least 2 to 4 months before the first benefits on hair growth can be observed.[4] Maximal effectiveness occurs after 12 months.[4]

Beard growth

Minoxidil has been studied for enhancement of facial hair or beard growth, including for transgender men.[5][49][50][6]

Nail problems

Minoxidil has been studied in the treatment of onychodystrophy (nail problems).[7][8] It has been assessed in at least 6 clinical studies for this purpose, with the employed formulations including 2 to 5% topical minoxidil and 1.25 to 2.5 mg/day oral minoxidil.[7] The drug has been found to increase the rate of nail growth, improve nail appearance, increase nail strength, and resolve yellow nail discoloration.[7][8]

Available forms

Minoxidil is available in the form of oral tablets, topical solution, topical foam, and topical spray.[21] The tablets include 2.5 and 10 mg forms, the solutions include 2% and 5% forms, and the foam and spray are both 5% concentration.[4][21][13] The topical solutions are formulated with polyethylene glycol (PEG) to enhance absorption of minoxidil.[21] The topical solution is often referred to as minoxidil topical solution (MTS) and the topical foam is known as minoxidil topical foam (MTF).[4]

Contraindications

In the case of oral minoxidil, absolute contraindications include pheochromocytoma, history of pericardial effusion or cardiac tamponade, history of pericarditis, history of pulmonary hypertension associated with mitral stenosis, hypersensitivity, and pregnancy and breastfeeding, whereas relative contraindications or precautions include hypotension (<90/60 mm hg), kidney impairment or failure, dialysis, history of heart attack, and history of tachycardia or other arrhythmia.[13][22][14][23] Congestive heart failure is an absolute or relative contraindication according to different sources.[13][23]

Side effects

Side effects of oral minoxidil may include salt retention, water retention and edema, rapid heartbeat, dizziness, lightheadedness, headaches, and hypertrichosis (excessive hair growth), among others.[13][20]

Topically applied minoxidil is generally well-tolerated, but common side effects include itching of the eyes, general itching, irritation at the treated area, and unwanted hair growth elsewhere on the body.[51] Alcohol and propylene glycol present in some topical preparations may dry the scalp, resulting in dandruff and contact dermatitis.[52]

Sublingual minoxidil may have reduced side effects with retained effectiveness compared to oral minoxidil.[53][54][55] This is due to less minoxidil sulfate being formed during first-pass metabolism and due to local activation of minoxidil into minoxidil sulfate within hair follicles.[53][54][55] In a preliminary clinical trial, no adverse effects or changes in blood pressure occurred with low-dose sublingual minoxidil.[54][55]

Oral minoxidil has been implicated in causing pericarditis, pericardial effusion, and pleural effusion.[13] Cardiac tamponade secondary to pericardial effusion, which can be life-threatening, is also known to occur.[13][22][56] Pericardial effusion has been found to occur in about 3% of people at hypertension doses.[13][57] This is usually associated with impaired renal function, connective tissue disease, uremic syndrome, congestive heart failure, or marked fluid retention, though cases without these potential risk factors have also been reported.[13][57] There have been case reports dating back to the 1980s describing these phenomena, including with oral minoxidil[58] and rarely even topical minoxidil.[56] However, these cardiovascular complications are much less common and rare with oral minoxidil at the low doses used to treat hair loss.[14][22][19] Potential symptoms indicating these minoxidil-induced cardiovascular complications include dyspnea (shortness of breath) and edema (fluid build-up), among others.[22][13]

Minoxidil has also been associated with a number of other types of cardiovascular complications, like ischemic heart disease, pulmonary hypertension, left ventricular hypertrophy, and specific electrocardiogram (ECG) abnormalities.[22][13] Cardiac lesions, such as focal necrosis of the papillary muscle and subendocardial areas of the left ventricle, have been observed in laboratory animals treated with minoxidil as well.[9]

KATP channel openers like levcromakalim and minoxidil among others have been strongly implicated in inducing headache and migraine.[20][59][60]

Pseudoacromegaly is an extremely rare side effect reported with large doses of oral minoxidil.[24] Oral minoxidil has been reported to cause coarsening of facial features in case reports.[36][25]

Overdose

Overdose of minoxidil has been reviewed.[13] In 2013 or 2014, a seven-year-old girl was admitted to a children's hospital in Toulouse in France after accidentally ingesting a teaspoon of Alopexy (a brand name for minoxidil in France). The child vomited constantly after ingestion and showed hypotension and tachycardia for 40 hours.[61] The authors of the report on the incident stressed that the product should be kept out of reach of children, and urged manufacturers to consider more secure child-resistant packaging.[62]

Interactions

Combination of oral minoxidil with guanethidine can result in profound orthostatic hypotension.[63][13]

Low-dose daily aspirin can reduce the effectiveness of topical minoxidil for hair loss.[64][36][65] This is thought to be because aspirin inhibits sulfotransferase activity and hence prevents conversion of minoxidil into its active form minoxidil sulfate.[64][36][65] Salicylic acid is also a sulfotransferase inhibitor and could likewise affect the effectiveness of topical minoxidil.[64][65] In addition, paracetamol (acetaminophen) is a sulfate scavenger and may inhibit minoxidil activation into minoxidil sulfate and effectiveness.[36][66]

Pharmacology

Pharmacodynamics

The mechanism by which minoxidil promotes hair growth is not fully understood. Minoxidil is an adenosine 5'-triphosphate (ATP)-sensitive potassium channel opener,[67] 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, minoxidil 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. Minoxidil is a prodrug that is converted by sulfation via the sulfotransferase enzyme SULT1A1 to its active form, minoxidil sulfate. The effect of minoxidil 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).[68] Minoxidil acts as an activator of the Kir6/SUR2 channel upon selective binding to SUR2.[69] The expression of SUR2B in dermal papilla cells might play a role in the production of adenosine.[68] Minoxidil 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.[70]

A number of in vitro effects of minoxidil 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.[27]

Minoxidil 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 minoxidil to generate a nitroxyl radical. It is presumed that this nitroxyl radical will be capable of reduction by glutathione to reform minoxidil. Such a process would cycle until the minoxidil 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.[71] Minoxidil 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 minoxidil increased blood vessel formation in a VEGF-dependent manner. Minoxidil inhibition of PHD occurs via interrupting ascorbate binding to iron.[72] The structural feature of positioning amines adjacent to nitric oxide may confer the ability of millimolar minoxidil to chelate iron, thereby inhibiting PHD. Minoxidil is capable of tetrahydrobiopterin inhibition as a cofactor for nitric oxide synthase.[73]

Minoxidil stimulates prostaglandin E2 production by activating COX-1[74] 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 minoxidil, which may enable hair follicles to grow continuously and maintain the anagen phase.[75]

Due to the anti-fibrotic activity of minoxidil inhibition of enzyme lysyl hydroxylase present in fibroblast may result in the synthesis of a hydroxylysine-deficient collagen. Minoxidil can also potentially stimulate elastogenesis in aortic smooth muscle cells, and in skin fibroblasts in a dose-dependent manner. In hypertensive rats, minoxidil increases elastin levels 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 1/2 (ERK 1/2)-activator protein 1 signaling pathway. ERK 1/2 increases, through elastin gene transcription, adequately cross-linked elastic fiber content synthesized by smooth muscle cells, and decreases the number of cells in the aorta.[76]

Minoxidil possesses α2-adrenergic receptor agonist activity,[77] stimulates the peripheral sympathetic nervous system (SNS) by way of carotid and aortic baroreceptor reflexes. Minoxidil 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 minoxidil, over time these values tend to normalize presumably because of accelerated metabolic clearance of aldosterone in association with hepatic vasodilation.[35]

Minoxidil may be involved in the inhibition of serotonin 5-HT2 receptors.[78]

Minoxidil might increase blood–tumor barrier permeability in a time-dependent manner by downregulating tight junction protein expression and this effect could be related to ROS/RhoA/PI3K/PKB signal pathway.[79] Minoxidil significantly increases ROS concentration when compared to untreated cells.

Minoxidil treatment resulted in a "0.22-fold change" for 5α-reductase 2 (p < 0.0001) in vitro. This antiandrogenic effect of minoxidil, shown by significant downregulation of 5α-reductase 2 gene expression in HaCaT cells, may be one of its mechanisms of action in alopecia.[80]

The effects of minoxidil have been found to mimic the symptoms of Cantú syndrome, which involves gain-of-function mutations in KATP channel subunits (specifically SUR2 and KIR6.1).[14][25][26] Examples of these minoxidil effects include hypertrichosis, pericardial effusions, pulmonary hypertension, edema, and coarsening of facial features, among others.[25] Relatedly, there has been concern that excessive doses of minoxidil and other KATP potassium channel openers might cause a "drug-induced Cantú syndrome".[25]

Pharmacokinetics

Absorption

Minoxidil is readily absorbed from the gastrointestinal tract with oral administration.[21] Its absorption from the gut is around 90% or more.[21][63][14] The drug reaches peak levels after about 30 to 60 minutes.[21][63][14][81] Following attainment of peak levels, concentrations of minoxidil rapidly decline.[63] Sublingual minoxidil is expected to have higher bioavailability than topical minoxidil.[53][82] Peak levels with sublingual administration occurred after 30 minutes.[55] The bioavailability of oral minoxidil is not affected by food and it can be taken in either a fasted or fed state.[83]

In the case of topical administration to the scalp, the absorption of minoxidil is only about 1.2 to 1.4%.[21] With this route, serum levels of minoxidil are usually less than 5 ng/mL and are frequently undetectable.[21] It has been predicted that application of 5% topical minoxidil twice to the entire scalp might be equivalent to a single 5.4 mg oral dose of minoxidil in terms of systemic exposure.[21][84] The stratum corneum of the scalp is saturated by minoxidil and acts as a reservoir for the drug.[4] This results in a continuous flow of minoxidil in the scalp, with absorption being completed after about 10 to 12 hours.[4] Based on these findings, topical minoxidil is generally applied twice daily.[4] A wet scalp has been found to increase the absorption of topical minoxidil.[4]

Peak levels of minoxidil with oral minoxidil were 16.8 ng/mL with 2.5 mg, 37.2 ng/mL with 5 mg, and 74.7 ng/mL with 10 mg doses.[83][81] Mean peak minoxidil levels with a single 0.45 mg dose of sublingual minoxidil were 1.62 ng/mL (range 0.3–5.3 ng/mL).[55] Circulating levels of 0.6 ng/mL with 2% solution and 1.6 ng/mL with 5% solution occur with topical minoxidil.[4] However, levels vary between individuals, with a range of undetectable to 7.5 ng/mL with 3% solution in 12 individuals in one study.[21][85] Significant cardiological and hemodynamic effects are said to occur with minoxidil when serum minoxidil levels exceed 20 ng/mL.[4][86]

Distribution

The volume of distribution of oral minoxidil is greater than 200 L.[83] Minoxidil does not cross the blood–brain barrier and hence is peripherally selective.[21][83][63] It shows minimal or negligible plasma protein binding.[21][83][63]

Metabolism

Minoxidil is a prodrug of minoxidil sulfate, which can be formed both systemically and locally within hair follicles.[21][4][66] This active metabolite is 14-fold more potent than minoxidil in stimulating cysteine incorporation in cultured rodent hair follicles ex vivo.[4][66] Similarly to minoxidil, it also stimulates hair follicle growth.[4][66] Minoxidil is sulfated into minoxidil sulfate by at least four cytosolic sulfotransferase enzymes found in skin, scalp, smooth muscle, liver, and fibroblasts.[4] The primary sulfotransferase involved in sulfation of minoxidil in hair follicles is SULT1A1, whereas in the liver, it is SULT2A1.[21][53] Expression of this enzyme has been found to predict the effectiveness of topical minoxidil.[21]

Oral minoxidil is subject to first-pass metabolism, including rapid and extensive metabolism in the liver.[4] A majority of orally administered minoxidil, about 90%, is metabolized in the liver via glucuronidation, hydroxylation, and sulfation, with glucuronidation being the primary metabolic pathway and minoxidil glucuronide being the predominant metabolite of minoxidil.[21][83][63][14] Conversely, topical minoxidil bypasses the first pass through the liver and is not subject to first-pass metabolism.[4] Similarly, sublingual minoxidil also bypasses first-pass metabolism.[53][54][82]

Elimination

Minoxidil is excreted almost exclusively (>97%) in urine.[4] About 10 to 15% is excreted in urine unchanged.[36] The elimination half-life of oral minoxidil is about 3 to 4 hours.[21][63][14] Conversely, the half-life of topical minoxidil is 22 hours on average.[4] Oral minoxidil is excreted within 12 to 20 hours in urine.[21] Despite this however, the hypotensive effect of oral minoxidil lasts approximately 72 hours following a single dose.[83] With discontinuation of topical minoxidil, about 95% of systemically absorbed minoxidil is excreted within 4 days.[21] The renal clearance of oral minoxidil is 352 mL/minute.[83]

Chemistry

Properties

Minoxidil is an odorless, white to off-white, crystalline powder (crystals from methanol-acetonitrile). When heated to decomposition it emits toxic fumes of nitrogen oxides. It decomposes at 259-261 °C.[87] Its solubility (mg/ml) is propylene glycol 75, methanol 44, ethanol 29, 2-propanol 6.7, dimethylsulfoxide 6.5, water 2.2, chloroform 0.5, acetone <0.5, ethyl acetate <0.5, diethyl ether <0.5, benzene <0.5, acetonitrile <0.5. The pKa of minoxidil is 4.61.

Synthesis

Another synthesis approach of Minoxidil[88]

Minoxidil, 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine, is synthesized from barbituric acid, the reaction of which with phosphorus oxychloride gives 2,4,6-trichloropyrimidine. Upon reaction with ammonium, this turns into 2,4-diamino-6-chloropyrimidine. Next, the resulting 2,4-diamino-6-chloropyrimidine undergoes a reaction with 2,4-dichlorophenol in the presence of potassium hydroxide, giving 2,4-diamino-6-(2,4-dichlorophenoxy)-pyrimidine. Oxidation of this product with 3-chloroperbenzoic acid gives 2,4-diamino-6-(2,4-dichlorophenoxy)pyrimidine-3-oxide, the 2,4-dichlorophenoxyl group of which is replaced with a piperidine group at high temperature, giving minoxidil.[89]

History

Initial development

A predecessor compound of minoxidil was developed in the late 1950s by the Upjohn Company (later became part of Pfizer) to treat ulcers. In trials using dogs, the compound did not cure ulcers but proved to be a powerful vasodilator. Upjohn synthesized over 200 variations of the compound, including the one it developed in 1963 and named minoxidil.[28] These studies resulted in the U.S. Food and Drug Administration (FDA) approving minoxidil (with the brand name Loniten) in the form of oral tablets to treat high blood pressure in 1979.[90][91]

Repurposing for hair growth

When Upjohn received permission from the U.S. Food and Drug Administration (FDA) to test the new drug as medicine for hypertension they approached Charles A. Chidsey, at the University of Colorado School of Medicine.[28] He conducted two studies,[92][93] the second study showing unexpected hair growth. Puzzled by this side-effect, Chidsey consulted Guinter Kahn (who while a dermatology resident at the University of Miami had been the first to observe and report hair development on patients using the minoxidil patch) and discussed the possibility of using minoxidil for treating hair loss.[citation needed]

Kahn, along with his colleague Paul J. Grant, had obtained a certain amount of minoxidil and conducted their own research, since they were first to make the side effect observation. Neither Upjohn or Chidsey at the time were aware of the side effect of hair growth.[94] The two doctors had been experimenting with a 1% solution of minoxidil mixed with several alcohol-based liquids.[95] Both parties filed patents to use minoxidil for hair loss prevention, which resulted in a decade-long trial between Kahn and Upjohn, which ended with Kahn's name included in a consolidated patent (U.S. #4,596,812 Charles A Chidsey, III and Guinter Kahn) in 1986 and royalties from the company to both Kahn and Grant.[94]

Meanwhile, the effect of minoxidil on hair loss prevention was so clear that in the 1980s physicians were prescribing Loniten off-label to their balding patients.[91]

In August 1988, the FDA approved minoxidil for treating baldness in men[91][95] under the brand name "Rogaine" (FDA rejected Upjohn's first choice, Regain, as misleading[96]). The agency concluded that although "the product will not work for everyone", 39% of the men studied had "moderate to dense hair growth on the crown of the head".[96] "Men's Rogaine", marketed by Johnson & Johnson went off-patent on January 20, 2006.[97]

In 1991, Upjohn made the product available for women.[95] "Women's Rogaine", marketed by Johnson & Johnson, went off-patent in February 2014.[97]

Non-topical formulations for hair growth

Low-dose oral minoxidil started to emerge as a treatment for hair loss in 2015 and after with the work of Rodney Sinclair and other researchers.[30][31][98][99][100] Subsequently, interest in and use of low-dose oral minoxidil for hair loss increased dramatically following the publication of an August 2022 New York Times article titled "An Old Medicine Grows New Hair for Pennies a Day, Doctors Say".[30][14][22][32][101][102][103][104] New non-topical formulations of minoxidil for hair loss, such as extended-release oral minoxidil and sublingual minoxidil, have been developed in the 2020s towards formal approval for treatment of hair loss and with improved efficacy and/or tolerability profiles.[19][15][18]

Society and culture

Economics

In February 1996, the FDA approved both the over-the-counter sale and the production of generic formulations of minoxidil.[91] Upjohn replied to that by lowering prices to half the price of the prescription drug[95] and by releasing a prescription 5% formula of Rogaine in 1997.[91][105] In 1998, a 5% formulation of minoxidil was approved for nonprescription sale by the FDA.[106] The 5% aerosol foam formula was approved for medical use in the US in 2006.[107][108] The generic versions of the 5% aerosol foam formula were approved in 2017.[109][110]

In 2017, a study of pharmacy prices in four states for 41 over-the-counter minoxidil products which were "gender-specified" found that the mean price for minoxidil solutions was the same for women and men even though the women's formulations were 2% and the men's were 5%, while the mean price for minoxidil foams, which were all 5%, was 40% higher for women. The authors noted this was the first time gender-based pricing had been shown for a medication.[111]

Brand names

As of June 2017, Minoxidil is sold under many brand names worldwide, including but not limited to: Alomax, Alopek, Alopexy, Alorexyl, Alostil, Aloxid, Aloxidil, Anagen, Apo-Gain, Axelan, Belohair, Boots Hair Loss Treatment, Botafex, Capillus, Carexidil, Coverit, Da Fei Xin, Dilaine, Dinaxcinco, Dinaxil, Ebersedin, Eminox, Folcare, Follixil, Guayaten, Hair Grow, Hair-Treat, Hairgain, Hairgaine, Hairgrow, Hairway, Headway, Inoxi, Ivix, Keranique, Lacovin, Locemix, Loniten, Lonnoten, Lonolox, Lonoten, Loxon, M E Medic, Maev-Medic, Mandi, Manoxidil, Mantai, Men's Rogaine, Minodil, Minodril, Minostyl, Minovital, Minox, Minoxi, Minoxidil, Minoxidilum, Minoximen, Minoxiten, Minscalp, Mintop, Modil, Morr, Moxidil, Neo-Pruristam, Neocapil, Neoxidil, Nherea, Nioxin, Noxidil, Oxofenil, Pilfud, Pilogro, Pilomin, Piloxidil, Re-Stim, Re-Stim+, Recrea, Regain, Regaine, Regaxidil, Regro, Regroe, Regrou, Regrowth, Relive, Renobell Locion, Reten, Rexidil, Rogaine, Rogan, Scalpmed, Si Bi Shen, Splendora, Superminox, Trefostil, Tricolocion, Tricoplus, Tricovivax, Tricoxane, Trugain, Tugain, Unipexil, Vaxdil, Vius, Women's Regaine, Xenogrow, Xtreme Boost, Xtreme Boost+, Xue Rui, Ylox, and Zeldilon.[112] It is also sold as a combination medication with amifampridine under the brand names Gainehair and Hair 4 U; and as a combination with tretinoin and clobetasol under the brand name Sistema GB.[112]

Research

Hair loss

See also: Chemistry:List of investigational hair loss drugs

An extended-release formulation of low-dose oral minoxidil is under development for treatment of hair loss.[15][113][16][17] It is being developed by Veradermics under the developmental code name VDPHL01.[15][113][16][17] As of September 2025, it is in phase 3 clinical trials for this indication.[15][16][17]

A low-dose sublingual formulation of minoxidil is under development for treatment of hair loss.[18][114][115] It is being developed by Samson Clinical.[18][114][115] As of September 2025, it is in phase 3 clinical trials for this indication.[18][114][115] The pharmacokinetics of this formulation are being studied.[116]

Finasteride/latanoprost/minoxidil (developmental code name TH-07 or TH07; Triple Hair) is a topical combination drug including minoxidil, finasteride, and latanoprost which is under development for the treatment of hair loss.[117][118] As of December 2023, it is in phase 2 clinical trials for this indication.[117]

AB-103 is a minoxidil sulfotransferase stimulant which enhances minoxidil conversion into its active form minoxidil sulfate in hair follicles and is under development as a topical medication for the treatment of hair loss.[119] Sulfotransferase activity in hair follicles has been associated with minoxidil's clinical effectiveness.[120][4] As of February 2024, AB-103 is in phase 3 clinical trials for this indication, although there have been no new updates since 2019.[119]

Other uses

Minoxidil is being investigated as a potential treatment for ovarian cancer.[121][122]

Toxicity to animals

Minoxidil is highly toxic to dogs and cats, even in doses as small as a drop or lick.[33] There are reported cases of cats dying shortly after coming in contact with minimal amounts of the substance.[34] There is no specific antidote, but lipid rescue has been used successfully.[123][124]

References

  1. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Loniten SmPC
  2. ↑ 2.0 2.1 Cite error: Invalid <ref> tag; no text was provided for refs named Regaine for Men SmPC
  3. ↑ 3.0 3.1 Cite error: Invalid <ref> tag; no text was provided for refs named Regaine for Women SmPC
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 4.20 4.21 4.22 4.23 4.24 4.25 "Minoxidil". Androgenetic Alopecia From A to Z. Cham: Springer International Publishing. 2022. pp. 11–39. doi:10.1007/978-3-031-08057-9_1. ISBN 978-3-031-08056-2. https://link.springer.com/10.1007/978-3-031-08057-9_1. Retrieved 23 October 2025. 
  5. ↑ 5.0 5.1 "Managing common dermatologic needs in transgender and gender-diverse adolescents". Current Pediatrics Reports 13. 2024. doi:10.1007/s40124-025-00344-y. PMID 40547400. 
  6. ↑ 6.0 6.1 "Efficacy and safety of topical 3% minoxidil for facial hair enhancement in transmen: a randomized, double-blind, placebo-controlled trial". The Journal of Dermatological Treatment 37 (1). December 2026. doi:10.1080/09546634.2026.2638637. PMID 41778417. 
  7. ↑ 7.0 7.1 7.2 7.3 "Minoxidil as a treatment for onychodystrophy: a systematic review". JAAD International 22: 46–48. October 2025. doi:10.1016/j.jdin.2025.05.014. PMID 40727639. 
  8. ↑ 8.0 8.1 8.2 "Minoxidil Beyond Hair: A Comprehensive Review of Its Effects on Nail Growth". Journal of Clinical Medicine 15 (5): 1792. February 2026. doi:10.3390/jcm15051792. PMID 41827209. 
  9. ↑ 9.0 9.1 "Minoxidil tablet". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ab30461c-f8c8-409d-9e24-d58ed8a34873. 
  10. ↑ "Minoxidil aerosol, foam". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=390aa2c9-de7f-4365-a03c-cbbf8e662b7c. 
  11. ↑ "Mens Rogaine Extra Strength Unscented- minoxidil solution". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ccaecec5-5348-4b24-9190-5464c50f6d80. 
  12. ↑ "Womens Rogaine Unscented- minoxidil solution". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bf0000c-95f3-4a4d-830b-f5ac1539823d. 
  13. ↑ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 13.11 13.12 13.13 13.14 https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/018154s026lbl.pdf
  14. ↑ 14.00 14.01 14.02 14.03 14.04 14.05 14.06 14.07 14.08 14.09 14.10 14.11 14.12 "Oral Minoxidil for Alopecia Treatment: Risks, Benefits, and Recommendations". Am J Clin Dermatol 27 (1): 101–119. January 2026. doi:10.1007/s40257-025-00990-4. PMID 41118052. 
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 "VDPHL". 9 September 2025. https://adisinsight.springer.com/drugs/800073330. 
  16. ↑ 16.0 16.1 16.2 16.3 "A New Oral Minoxidil May Be FDA-Approved for Hair Loss: What to Know". Harper's BAZAAR. 16 October 2025. https://www.harpersbazaar.com/beauty/hair/a69050608/new-hair-loss-treatment-oral-minoxidil/. Retrieved 23 October 2025. 
  17. ↑ 17.0 17.1 17.2 17.3 "A First-of-Its-Kind Hair Loss Pill Could Be on Its Way". 17 October 2025. https://www.allure.com/story/vdphl01-hair-loss-medication-in-development. 
  18. ↑ 18.0 18.1 18.2 18.3 18.4 18.5 "Sublingual minoxidil". 22 September 2025. https://adisinsight.springer.com/drugs/800083976. 
  19. ↑ 19.0 19.1 19.2 19.3 19.4 19.5 19.6 19.7 "Expanding the therapeutic landscape of minoxidil for androgenetic alopecia: topical, oral and sublingual formulations". Frontiers in Pharmacology 16. 2025. doi:10.3389/fphar.2025.1718208. PMID 41695992. 
  20. ↑ 20.0 20.1 20.2 "The ATP sensitive potassium channel (KATP) is a novel target for migraine drug development". Front Mol Neurosci 16. 2023. doi:10.3389/fnmol.2023.1182515. PMID 37456521. 
  21. ↑ 21.00 21.01 21.02 21.03 21.04 21.05 21.06 21.07 21.08 21.09 21.10 21.11 21.12 21.13 21.14 21.15 21.16 21.17 21.18 21.19 Cite error: Invalid <ref> tag; no text was provided for refs named GuptaTalukderVenkataraman2022
  22. ↑ 22.0 22.1 22.2 22.3 22.4 22.5 22.6 22.7 "Low dose oral minoxidil and the conundrum of cardiovascular complications". Dermatology Online Journal 29 (4). August 2023. doi:10.5070/D329461861. PMID 37921812. 
  23. ↑ 23.0 23.1 23.2 23.3 23.4 "Low-Dose Oral Minoxidil Initiation for Patients With Hair Loss: An International Modified Delphi Consensus Statement". JAMA Dermatology 161 (1): 87–95. January 2025. doi:10.1001/jamadermatol.2024.4593. PMID 39565602. https://escholarship.org/uc/item/2pp1b5gc. 
  24. ↑ 24.0 24.1 "Pseudoacromegaly induced by the long-term use of minoxidil". Journal of the American Academy of Dermatology 48 (6): 962–965. June 2003. doi:10.1067/mjd.2003.325. PMID 12789195. 
  25. ↑ 25.0 25.1 25.2 25.3 25.4 25.5 "Kir6.1 and SUR2B in Cantú syndrome". American Journal of Physiology. Cell Physiology 323 (3). September 2022. doi:10.1152/ajpcell.00154.2022. PMID 35876283. "As mentioned earlier, the hair-growth-promoting properties of minoxidil were clear from initial development. [...] Of concern, if excessive doses are used, even topically, there is the potential for minoxidil to have systemic effects—precipitating a possible "drug-induced Cantú syndrome." Indeed [pulmonary hypertension (PH)], edema, coarsening of facial features, and even reopening of the ductus arteriosus are associated with the Kir6.1/SUR2B active [potassium channel openers (KCOs)] minoxidil and diazoxide (156–158). Multiple KCOs induce and prolong anagen, the rapidly dividing stage of hair, in cultured follicles to promote growth, which can be reversed by the KATP inhibitor tolbutamide (86–88, 159). It is possible that CS-associated mutations have the same hair growth cycle effects, though this requires clarification. Thinking more broadly about the electrical consequences, KATP activation versus voltage-gated calcium channel (VGCC) activation would be expected to have opposing electrophysiological effects, and interestingly Timothy syndrome, caused by gain-of-function mutations in the VGCC, CaV1.2 is associated with baldness at birth (160), potentially the reverse mechanistic phenomenon.". 
  26. ↑ 26.0 26.1 26.2 "Skin and hair abnormalities of Cantu syndrome: A congenital hypertrichosis due to a genetic alteration mimicking the pharmacological effect of minoxidil". The Journal of Dermatology 47 (3): 306–310. March 2020. doi:10.1111/1346-8138.15216. PMID 31907964. 
  27. ↑ 27.0 27.1 "Minoxidil: mechanisms of action on hair growth". The British Journal of Dermatology 150 (2): 186–194. February 2004. doi:10.1111/j.1365-2133.2004.05785.x. PMID 14996087. 
  28. ↑ 28.0 28.1 28.2 28.3 28.4 "Guinter Kahn, Inventor of Baldness Remedy, Dies at 80". The New York Times. September 19, 2014. https://www.nytimes.com/2014/09/20/business/guinter-kahn-inventor-of-baldness-remedy-dies-at-80.html. 
  29. ↑ "The history of the development of minoxidil". Clin Dermatol 6 (4): 132–147. 1988. doi:10.1016/0738-081x(88)90078-8. PMID 3063368. 
  30. ↑ 30.0 30.1 30.2 30.3 30.4 "An Old Medicine Grows New Hair for Pennies a Day, Doctors Say". The New York Times. August 18, 2022. https://www.nytimes.com/2022/08/18/health/minoxidil-hair-loss-pills.html. 
  31. ↑ 31.0 31.1 Rodney Sinclair (16 May 2015). "Female pattern hair loss: Combination therapy with low dose oral minoxidil and spironolactone". 2015 Annual Meeting of the Australasian Society for Dermatology Research. https://asdr-2015.p.asnevents.com.au/days/2015-05-16/abstract/25688. 
  32. ↑ 32.0 32.1 "Changes in Minoxidil Prescribing After Media Attention About Oral Use for Hair Loss". JAMA Network Open 6 (5). May 2023. doi:10.1001/jamanetworkopen.2023.12477. PMID 37159202. 
  33. ↑ 33.0 33.1 "Topical Minoxidil Exposures and Toxicoses in Dogs and Cats: 211 Cases (2001-2019)". Journal of the American Animal Hospital Association 57 (5): 225–231. September 2021. doi:10.5326/JAAHA-MS-7154. PMID 34370845. 
  34. ↑ 34.0 34.1 "Suspected toxicosis after topical administration of minoxidil in 2 cats". Journal of Veterinary Emergency and Critical Care 14 (4): 287–292. November 2004. doi:10.1111/j.1476-4431.2004.04014.x. 
  35. ↑ 35.0 35.1 35.2 35.3 "Minoxidil: an underused vasodilator for resistant or severe hypertension". Journal of Clinical Hypertension 6 (5): 283–287. May 2004. doi:10.1111/j.1524-6175.2004.03585.x. PMID 15133413. 
  36. ↑ 36.0 36.1 36.2 36.3 36.4 36.5 36.6 36.7 "Summation and recommendations for the safe and effective use of topical and oral minoxidil". Journal of the American Academy of Dermatology 93 (2): 457–465. August 2025. doi:10.1016/j.jaad.2025.04.016. PMID 40216195. https://escholarship.org/uc/item/5d42s0q7. 
  37. ↑ 37.0 37.1 "Androgenetic alopecia: an evidence-based treatment update". American Journal of Clinical Dermatology 15 (3): 217–230. July 2014. doi:10.1007/s40257-014-0077-5. PMID 24848508. 
  38. ↑ 38.0 38.1 "Sublingual minoxidil increases fibre diameter in male androgenetic alopecia: a proxy for reversal of hair follicle miniaturization". Clinical and Experimental Dermatology 50 (7): 1362–1365. June 2025. doi:10.1093/ced/llaf012. PMID 39774750. 
  39. ↑ "Medical treatments for balding in men". American Family Physician 59 (8): 2189–2194, 2196. April 1999. PMID 10221304. https://www.aafp.org/link_out?pmid=10221304. 
  40. ↑ "Oral minoxidil treatment for hair loss: A review of efficacy and safety". Journal of the American Academy of Dermatology 84 (3): 737–746. March 2021. doi:10.1016/j.jaad.2020.06.1009. PMID 32622136. 
  41. ↑ "Safety of low-dose oral minoxidil treatment for hair loss. A systematic review and pooled-analysis of individual patient data". Dermatologic Therapy 33 (6). November 2020. doi:10.1111/dth.14106. PMID 32757405. 
  42. ↑ "Low-dose oral minoxidil as treatment for non-scarring alopecia: a systematic review". International Journal of Dermatology 59 (8): 1013–1019. August 2020. doi:10.1111/ijd.14933. PMID 32516434. 
  43. ↑ "Compliance to Topical Minoxidil and Reasons for Discontinuation among Patients with Androgenetic Alopecia". Dermatology and Therapy 13 (5): 1157–1169. May 2023. doi:10.1007/s13555-023-00919-x. PMID 37012528. 
  44. ↑ "Is topical minoxidil solution effective on androgenetic alopecia in routine daily practice?". The Journal of Dermatological Treatment 18 (5): 268–270. 2007. doi:10.1080/09546630701383727. PMID 17917938. 
  45. ↑ "Low-dose oral minoxidil (LDOM) and topical minoxidil: consensus recommendations for managing male and female pattern Hair loss in Hair transplant patients using a modified delphi process". Expert Opinion on Pharmacotherapy 27 (3): 253–261. March 2026. doi:10.1080/14656566.2026.2642216. PMID 41782304. 
  46. ↑ 46.0 46.1 "There Is a Positive Dose-Dependent Association between Low-Dose Oral Minoxidil and Its Efficacy for Androgenetic Alopecia: Findings from a Systematic Review with Meta-Regression Analyses". Skin Appendage Disorders 8 (5): 355–361. September 2022. doi:10.1159/000525137. PMID 36161084. 
  47. ↑ "Review of oral minoxidil as treatment of hair disorders: in search of the perfect dose". Journal of the European Academy of Dermatology and Venereology 35 (7): 1485–1492. July 2021. doi:10.1111/jdv.17216. PMID 33660357. 
  48. ↑ "Sublingual Minoxidil 5 mg versus Oral Minoxidil 5 mg for male androgenetic alopecia: A double-blind randomized clinical trial". Journal of the European Academy of Dermatology and Venereology 39 (8). August 2025. doi:10.1111/jdv.20508. PMID 39688293. 
  49. ↑ "Efficacy of topical minoxidil in enhancing beard growth in a group of transgender assigned female at birth individuals on gender affirming hormone therapy". Journal of Endocrinological Investigation 47 (11): 2843–2850. November 2024. doi:10.1007/s40618-024-02373-8. PMID 38644453. 
  50. ↑ "Case Report: Successful Use of Minoxidil to Promote Facial Hair Growth in an Adolescent Transgender Male". Frontiers in Endocrinology 12. 2021. doi:10.3389/fendo.2021.725269. PMID 34659117. 
  51. ↑ "Rogaine Side Effects". Drugs.com. https://www.drugs.com/sfx/rogaine-side-effects.html. 
  52. ↑ "Dandruff and Seborrheic Dermatitis". US Pharmacist 26 (4): 16–24. 2001. http://www.medscape.com/viewarticle/407641. 
  53. ↑ 53.0 53.1 53.2 53.3 53.4 "Comprehensive review of oral minoxidil in alopecia". Journal of Cosmetic Dermatology 21 (11): 5527–5531. November 2022. doi:10.1111/jocd.15324. PMID 36065675. "Sublingual doses of 0.45 and 0.90 mg minoxidil were evaluated by Sinclair et al.31 as sublingual route bypasses hepatic first-pass metabolism, sublingual minoxidil could be used to increase follicular minoxidil sulfate bioavailability and thus hair growth. As hepatic sulphation of minoxidil enhances the hemodynamic effect, sublingual minoxidil would decrease the hemodynamic adverse effects and consequently improve safety profile.". 
  54. ↑ 54.0 54.1 54.2 54.3 "What's New in Therapy for Male Androgenetic Alopecia?". American Journal of Clinical Dermatology 24 (1): 15–24. January 2023. doi:10.1007/s40257-022-00730-y. PMID 36169916. "Sublingual minoxidil has been proposed as an alternative route of administration to obtain the same improvement in hair density with lower doses. Moreover, a sublingual dose would avoid hepatic first-pass metabolism and may reduce the AEs. The results of the first phase 1B clinical trial have recently been published [34]. Patients receiving sublingual minoxidil 0.45 mg daily had a significant improvement in hair density after 6 months. Higher doses (1.35 and 4.05 mg) were also effective. None of the patients reported AEs and investigators did not find significant changes in blood pressure.". 
  55. ↑ 55.0 55.1 55.2 55.3 55.4 "Sublingual minoxidil for the treatment of male and female pattern hair loss: a randomized, double-blind, placebo-controlled, phase 1B clinical trial". Journal of the European Academy of Dermatology and Venereology 36 (1). January 2022. doi:10.1111/jdv.17623. PMID 34420241. 
  56. ↑ 56.0 56.1 "Signs of early cardiac tamponade induced by Minoxidil". The American Journal of Emergency Medicine 40. February 2021. doi:10.1016/j.ajem.2020.07.050. PMID 32778436. 
  57. ↑ 57.0 57.1 "Pericardial disorders occurring during open-label study of 1,869 severely hypertensive patients treated with minoxidil". Journal of Cardiovascular Pharmacology 2 Suppl 2. 1980. doi:10.1097/00005344-198000022-00016. PMID 6156358. 
  58. ↑ "Pericardial effusion associated with minoxidil therapy". Archives of Internal Medicine 141 (1): 69–71. January 1981. doi:10.1001/archinte.1981.00340010061014. PMID 7447585. 
  59. ↑ "Advances in understanding migraine for the development of novel pharmacotherapies: the use of human provocation migraine models". Expert Opin Pharmacother 26 (9): 1021–1040. June 2025. doi:10.1080/14656566.2025.2505231. PMID 40353527. 
  60. ↑ "De novo nitric oxide synthesis drives tactile hypersensitivity induced by ATP-sensitive potassium channel opening in mice: relevance to migraine and other headache disorders". Pain. April 2026. doi:10.1097/j.pain.0000000000003955. PMID 42048631. 
  61. ↑ "Minoxidil topical solution: an unsafe product for children". Pediatric Emergency Care 31 (1): 44–46. January 2015. doi:10.1097/PEC.0000000000000301. PMID 25426682. 
  62. ↑ "Hair loss treatment may be dangerous to kids". Reuters. December 10, 2014. https://www.reuters.com/article/us-side-effects-children-minoxidil-idUSKBN0JO2DB20141210. 
  63. ↑ 63.0 63.1 63.2 63.3 63.4 63.5 63.6 63.7 "Loniten minoxidil tablets, USP". https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=739988. 
  64. ↑ 64.0 64.1 64.2 "Minoxidil and its use in hair disorders: a review". Drug Design, Development and Therapy 13: 2777–2786. 2019. doi:10.2147/DDDT.S214907. PMID 31496654. "Salicylate and aspirin can inhibit sulfotransferase. A recent study showed that the follicular enzymatic activity decreased following 14 days of low-dose aspirin use. Thus, prior or concomitant use of aspirin decreases the clinical response to topical minoxidil.11". 
  65. ↑ 65.0 65.1 65.2 "Low-dose daily aspirin reduces topical minoxidil efficacy in androgenetic alopecia patients". Dermatologic Therapy 31 (6). November 2018. doi:10.1111/dth.12741. PMID 30226287. 
  66. ↑ 66.0 66.1 66.2 66.3 "Minoxidil sulfate is the active metabolite that stimulates hair follicles". The Journal of Investigative Dermatology 95 (5): 553–557. November 1990. doi:10.1111/1523-1747.ep12504905. PMID 2230218. 
  67. ↑ "The effects of the potassium channel opener minoxidil on renal electrolytes transport in the loop of henle". The Journal of Pharmacology and Experimental Therapeutics 304 (2): 833–840. February 2003. doi:10.1124/jpet.102.043380. PMID 12538840. 
  68. ↑ 68.0 68.1 "Minoxidil-induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil". The Journal of Investigative Dermatology 117 (6): 1594–1600. December 2001. doi:10.1046/j.0022-202x.2001.01570.x. PMID 11886528. "The expression of sulfonylurea receptor 2B and of the adenosine A1, A2A, and A2B receptors was detected in dermal papilla cells by means of reverse transcription polymerase chain reaction analysis.". 
  69. ↑ "Repurposing Kir6/SUR2 Channel Activator Minoxidil to Arrests Growth of Gynecologic Cancers". Frontiers in Pharmacology 11. May 8, 2020. doi:10.3389/fphar.2020.00577. PMID 32457608. 
  70. ↑ "[Hair growth effect of minoxidil]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 119 (3): 167–174. March 2002. doi:10.1254/fpj.119.167. PMID 11915519. 
  71. ↑ "Effects of minoxidil on cell proliferation and intracellular glutathione status of murine (L929) fibroblasts". Proceedings of the 1st European Conference on Advances in Wound Management, Cardiff, 4-6 September 1991. Macmillan Magazines. 1992. pp. 122–128. ISBN 978-0-333-58645-7. 
  72. ↑ "Minoxidil Induction of VEGF Is Mediated by Inhibition of HIF-Prolyl Hydroxylase". International Journal of Molecular Sciences 19 (1): 53. December 2017. doi:10.3390/ijms19010053. PMID 29295567. 
  73. ↑ Gross SS, "Blocking utilization of tetrahydrobiopterin to block induction of nitric oxide synthesis", US patent 5874433, published 1999-02-23
  74. ↑ "HMGB1 promotes hair growth via the modulation of prostaglandin metabolism". Scientific Reports 9 (1). April 2019. doi:10.1038/s41598-019-43242-2. PMID 31040377. Bibcode: 2019NatSR...9.6660H. 
  75. ↑ "Minoxidil and its use in hair disorders: a review". Drug Design, Development and Therapy 13: 2777–2786. 2019. doi:10.2147/DDDT.S214907. PMID 31496654. 
  76. ↑ "Minoxidil versus placebo in the treatment of arterial wall hypertrophy in children with Williams Beuren Syndrome: a randomized controlled trial". BMC Pediatrics 19 (1). May 2019. doi:10.1186/s12887-019-1544-1. PMID 31138170. 
  77. ↑ "Evidence for alpha 2-adrenoceptor agonist activity of minoxidil". The Journal of Pharmacy and Pharmacology 49 (9): 935–937. September 1997. doi:10.1111/j.2042-7158.1997.tb06139.x. PMID 9306265. 
  78. ↑ "Interactions of minoxidil with vasoconstrictive agents in isolated rat tail artery". Acta Poloniae Pharmaceutica 52 (3): 253–256. May 1995. PMID 8960256. 
  79. ↑ "Minoxidil sulfate induced the increase in blood-brain tumor barrier permeability through ROS/RhoA/PI3K/PKB signaling pathway". Neuropharmacology 75: 407–415. December 2013. doi:10.1016/j.neuropharm.2013.08.004. PMID 23973310. 
  80. ↑ "Minoxidil Acts as an Antiandrogen: A Study of 5α-reductase Type 2 Gene Expression in a Human Keratinocyte Cell Line". Acta Dermatovenerologica Croatica 25 (4): 271–275. December 2017. PMID 30064598. https://hrcak.srce.hr/192895. 
  81. ↑ 81.0 81.1 "The pharmacokinetics of 2.5- to 10-mg oral doses of minoxidil in healthy volunteers". Journal of Clinical Pharmacology 29 (2): 162–167. February 1989. doi:10.1002/j.1552-4604.1989.tb03307.x. PMID 2715373. 
  82. ↑ 82.0 82.1 "Treatment of male and female pattern hair loss with sublingual minoxidil: a retrospective case-series of 64 patients". Journal of the European Academy of Dermatology and Venereology 34 (12). December 2020. doi:10.1111/jdv.16616. PMID 32386429. 
  83. ↑ 83.0 83.1 83.2 83.3 83.4 83.5 83.6 83.7 "Low-Dose Oral Minoxidil for Alopecia: A Comprehensive Review". Skin Appendage Disorders 9 (6): 423–437. December 2023. doi:10.1159/000531890. PMID 38376087. 
  84. ↑ "Percutaneous absorption of minoxidil in man". Archives of Dermatology 121 (2): 203–206. February 1985. doi:10.1001/archderm.1985.01660020061018. PMID 3977334. 
  85. ↑ "Double-blind, placebo-controlled evaluation of topical minoxidil in extensive alopecia areata". Journal of the American Academy of Dermatology 16 (3 Pt 2): 730–736. March 1987. doi:10.1016/s0190-9622(87)70095-4. PMID 3549809. 
  86. ↑ "Hemodynamic effects of minoxidil following intravenous infusions in untreated hypertensive patients.". Clinical Pharmacology & Therapeutics 59 (2): 166. 1996. doi:10.1038/sj.clpt.1996.162. ISSN 0009-9236. 
  87. ↑ "COMPOUND SUMMARY Minoxidil". https://pubchem.ncbi.nlm.nih.gov/compound/Minoxidil#section=Chemical-and-Physical-Properties. 
  88. ↑ "A new approach to triaminopyrimidine n-oxides". The Journal of Organic Chemistry 40 (22): 3304–3306. October 1975. doi:10.1021/jo00910a040. PMID 1185310. 
  89. ↑ "Antihypertensive Drugs". Synthesis of Essential Drugs. 2006. pp. 295–310. doi:10.1016/B978-044452166-8/50022-4. ISBN 978-0-444-52166-8. 
  90. ↑ "Loniten: FDA-Approved Drugs". https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=018154. 
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  98. ↑ Rodney D. Sinclair (21 November 2015). "Female Pattern Hair Loss: Combination Therapy With Low Dose Oral Minoxidil and Spironolactone". 9th World Congress for Hair Research, November 18-21, 2015, Miami, Florida, USA. https://www.registration123.com/NAHRS/HAIR2015/media/pdf/AbstractBook_WCHR2015.pdf#page=64. 
  99. ↑ "Treatment of permanent chemotherapy-induced alopecia with low dose oral minoxidil". The Australasian Journal of Dermatology 57 (4). November 2016. doi:10.1111/ajd.12350. PMID 25966934. 
  100. ↑ "Treatment of monilethrix with oral minoxidil". JAAD Case Reports 2 (3): 212–215. May 2016. doi:10.1016/j.jdcr.2016.02.011. PMID 27284572. 
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  103. ↑ "How Media Coverage of Oral Minoxidil for Hair Loss Has Impacted Prescribing Habits". Cutis 113 (6): 269–270. June 2024. doi:10.12788/cutis.1033. PMID 39082999. 
  104. ↑ "Hair Loss Treatments: A Google Trends Analysis Worldwide of the Past 5 Years (2018–2023)". Skin Appendage Disorders 12 (1): 46–49. 17 July 2025. doi:10.1159/000547418. ISSN 2296-9195. PMID 42093754. 
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  108. ↑ "Rogaine: FDA-Approved Drugs". https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021812. 
  109. ↑ "Minoxidil: FDA-Approved Drugs". https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=208092. 
  110. ↑ "CDER 2017 First Generic Drug Approvals". February 20, 2018. https://www.fda.gov/drugs/first-generic-drug-approvals/2017-first-generic-drug-approvals. 
  111. ↑ "Association Between Gender and Drug Cost for Over-the-Counter Minoxidil". JAMA Dermatology 153 (8): 825–826. August 2017. doi:10.1001/jamadermatol.2017.1394. PMID 28593214. 
  112. ↑ 112.0 112.1 "International brand names for minoxidil". Drugs.com. https://www.drugs.com/international/minoxidil.html. 
  113. ↑ 113.0 113.1 "Extended-Release Minoxidil Shows Promise in AGA". 23 October 2025. https://www.dermatologytimes.com/view/extended-release-minoxidil-shows-promise-in-aga. 
  114. ↑ 114.0 114.1 114.2 Samson Clinical (6 August 2025). "First Patient Randomised in Samson Clinical Phase III Sublingual Minoxidil Trial for Male Pattern Hair Loss (Androgenetic Alopecia)". https://www.prnewswire.com/news-releases/first-patient-randomised-in-samson-clinical-phase-iii-sublingual-minoxidil-trial-for-male-pattern-hair-loss-androgenetic-alopecia-302523124.html. 
  115. ↑ 115.0 115.1 115.2 ClinicalTrials.gov. July 23, 2025. https://clinicaltrials.gov/study/NCT06924632. Retrieved 29 October 2025. 
  116. ↑ Phase 1 Pharmacokinetic Study of Minoxidil SL Tablets (A Phase 1 Randomized, Double Blind, Crossover Pharmacokinetic Study of Minoxidil Sublingual Tablets in Adult Male and Female Healthy Volunteers). February 13, 2025. https://clinicaltrials.gov/study/NCT06679556. Retrieved 17 January 2026. 
  117. ↑ 117.0 117.1 "Finasteride/latanoprost/minoxidil". 19 December 2023. https://adisinsight.springer.com/drugs/800071574. 
  118. ↑ "TH07 - A New Novel Topical Treatment for Androgenic Alopecia". International Journal of Trichology 15 (6): 241–247. 2023. doi:10.4103/ijt.ijt_145_22. PMID 39600423. 
  119. ↑ 119.0 119.1 "AB 103". 27 February 2024. https://adisinsight.springer.com/drugs/800052659. 
  120. ↑ "Minoxidil in the treatment of androgenetic alopecia". Dermatologic Therapy 31 (5). September 2018. doi:10.1111/dth.12686. PMID 30155952. 
  121. ↑ Clinical trial number NCT05272462 for "Oral Minoxidil for the Treatment of Recurrent Platinum Resistant Epithelial Ovarian Cancer" at ClinicalTrials.gov
  122. ↑ "Repurposing Kir6/SUR2 Channel Activator Minoxidil to Arrests Growth of Gynecologic Cancers". Front Pharmacol 11. 2020. doi:10.3389/fphar.2020.00577. PMID 32457608. 
  123. ↑ "Successful management of minoxidil 5% toxicosis in 2 cats from the same household". Journal of Veterinary Emergency and Critical Care 33 (4): 454–459. 2023. doi:10.1111/vec.13296. PMID 37222073. 
  124. ↑ "Successful management of minoxidil toxicosis in a dog". Journal of the American Veterinary Medical Association 252 (2): 222–226. January 2018. doi:10.2460/javma.252.2.222. PMID 29319439. 



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