|Systematic (IUPAC) name|
|Routes||Oral / topical|
|ATC code||C02 D11|
|PDB ligand ID||MXD (, )|
|Mol. mass||209.251 g/mol|
|(what is this?)|
Minoxidil is an antihypertensive vasodilator medication. It also slows or stops hair loss and promotes hair regrowth. Now off-patent, it is available over-the-counter for the treatment of androgenic alopecia.
Minoxidil is widely used for the treatment of hair loss. It has been proven clinically effective in both the prevention of loss and in establishing varying degrees of hair re-growth in males and females suffering pattern baldness. Minoxidil must be used indefinitely for continued support of existing hair follicles and the maintenance of any experienced hair regrowth.
Minoxidil is generally well tolerated, but common side effects include burning or irritation of the eye, itching, redness or irritation at the treated area, as well as unwanted hair growth elsewhere on the body. Users should discontinue treatment and seek medical attention right away if they experience any of the following serious side effects: severe allergic reactions (e.g. rash, hives, itching, difficulty breathing, tightness in the chest, or swelling of the mouth, face, lips, or tongue), chest pain, dizziness, fainting, tachycardia (rapid heartbeat), sudden and unexplained weight gain, or swelling of the hands and feet. Hair loss is a common side effect of minoxidil treatment. Manufacturers note that minoxidil-induced hair loss is a common side effect and describe the process as "shedding". Although this phenomenon demonstrates that minoxidil is indeed affecting hair follicles, manufacturers offer no guarantee that the new hair loss will be replaced with hair growth. The speculated reason for this shedding is the encouragement of hairs already in the telogen phase to shed early.
Alcohol and propylene glycol present in some topical preparations may dry the scalp, resulting in dandruff and contact dermatitis. Some formulations of minoxidil substitute lipid Nanosomes in order to reduce contact dermatitis from the alcohol and propylene glycol vehicle.
Side effects of oral minoxidil may include swelling of the face and extremities, rapid and irregular heartbeat, lightheadedness, cardiac lesions, and focal necrosis of the papillary muscle and subendocardial areas of the left ventricle. There have been cases of allergic reactions to minoxidil or the non-active ingredient propylene glycol, which is found in some topical minoxidil formulations. Pseudoacromegaly is an extremely rare side effect reported with large doses of oral minoxidil.
Mechanism of action
The mechanism by which minoxidil promotes hair growth is not fully understood. Minoxidil contains the nitric oxide chemical functional group and may act as a nitric oxide agonist. Similarly, minoxidil is a potassium channel opener, causing hyperpolarization of cell membranes. Minoxidil is less effective when there is a large area of hair loss. 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. Minoxidil is also a vasodilator. Hypothetically, by widening blood vessels and opening potassium channels, it allows more oxygen, blood, and nutrients to the follicle. 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 pro-drug activated by sulfation via the sulfotransferase (SULT1A1). Several studies demonstrated that the activity of sulfotransferase in hair follicles predict minoxidil response in the treatment of hair loss. Due to the low efficacy of minoxidil to re-grow hair (30-40% experience re-growth) and the long duration required to observe hair re-growth, a medical test to identify non-responders prior to initiating therapy would have great clinical significance. Two clinical studies are being conducted in the US for a medical device that may allow patients to determine if they are likely to fail minoxidil therapy.
Originally, minoxidil was used exclusively as an oral drug (with the trade name 'Loniten') to treat high blood pressure. However, it was discovered to have an interesting side effect: hair growth. Minoxidil may cause increased growth or darkening of fine body hairs, or in some cases, significant hair growth. When the medication is discontinued, the hair loss will return to normal rate within 30 to 60 days. Upjohn Corporation produced a topical solution that contained 2% minoxidil to be used to treat baldness and hair loss, under the brand name Rogaine in the United States and Canada, and Regaine in Europe and the Asia-Pacific. The patent on minoxidil expired February 11, 1996. Treatments usually include a 5% concentration solution that is designed for men, and a 2% concentration solution for women. While the drug is available in the United Kingdom, it cannot be prescribed on the NHS, so patients must either buy it over-the-counter, or have a private prescription for it.
Minoxidil needs to be applied twice daily, and may be used indefinitely for continued support of existing hair follicles and the maintenance of any experienced hair regrowth. To achieve maximum effect, the solution should be in contact with the scalp for at least 4 hours before allowing hair to get wet. Minoxidil stimulates hair follicles and growth, but does not reduce dihydrotestosterone (DHT) or the enzyme responsible for its accumulation around the hair follicle, 5-alpha reductase, which is the primary mediator of male pattern baldness in genetically susceptible individuals. Therefore, when treatment is stopped, the DHT has its expected effect of shrinking and ultimately destroying the genetically predisposed hair follicles.
An expeditious synthesis starts with the cyanomalonamide (1); this is then converted to its methyl enol ether (2), for example, by reaction with trimethyloxonium tetrafluoroborate. Reaction of that intermediate with cyanamide leads to the imine (3).
Condensation with hydroxylamine can occur at either cyano group; for clarity, only one alternative is shown. Addition to that on nitrogen will lead to the formation of the hypothetical hydroxyguanidine (4). Addition to the remaining nitrile leads to minoxidil (5) after bond rearrangement.
Minoxidil is marketed under many trade names, including Avogain, Rogaine, Regaine, Neocapil, Lipogaine, Avacor Physician's Formulation, Kirkland, Tugain, Loniten (oral), Mintop, Amexidil, Vanarex, Keranique and Obabo.
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