Minoxidil

Minoxidil
A space filling model of the molecule.
Clinical data
Trade names Rogaine
AHFS/Drugs.com Monograph
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		 By mouth / topical
    ATC code
    Legal status
    Legal status
    • UK: P (Pharmacy medicines) (for topical use, otherwise POM. Cannot be prescribed on the NHS)
    • US: OTC Rx only for by mouth form
    Pharmacokinetic data
    Metabolism Primarily hepatic
    Elimination half-life 4.2 h
    Excretion renal
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    PDB ligand
    ECHA InfoCard 100.048.959 Edit this at Wikidata
    Chemical and physical data
    Formula C9H15N5O
    Molar mass 209.251 g/mol
    3D model (JSmol)
    Melting point 248 °C (478 °F)
    Solubility in water <1 mg/mL (20 °C)
     &#9746;N&#9745;Y (what is this?)  (verify)

    Minoxidil is an antihypertensive vasodilator medication and is used to treat hair loss. It is available as a generic medication and over the counter for the treatment of androgenic alopecia, a form of hair loss, in people.[4]

    Medical uses

    Minoxidil, applied topically, is widely used for the treatment of hair loss. It is effective in helping promote hair growth in people with androgenic alopecia regardless of sex.[5] About 40% of men experience hair regrowth after 3–6 months.[6] Minoxidil must be used indefinitely for continued support of existing hair follicles and the maintenance of any experienced hair regrowth.[4]

    Its effect in people with alopecia areata is unclear.[7]

    Side effects

    Minoxidil is generally well tolerated, but common side effects include burning or irritation of the eye, itching, redness or irritation at the treated area, and unwanted hair growth elsewhere on the body. Exacerbation of hair loss/alopecia has been reported.[8][9] Severe allergic reactions may include rash, hives, itching, difficulty breathing, tightness in the chest, swelling of the mouth, face, lips, or tongue, chest pain, dizziness, fainting, tachycardia, headache, sudden and unexplained weight gain, or swelling of the hands and feet.[10] Temporary hair loss is a common side effect of minoxidil treatment.[11] Manufacturers note that minoxidil-induced hair loss is a common side effect and describe the process as "shedding".

    Alcohol and propylene glycol present in some topical preparations may dry the scalp, resulting in dandruff and contact dermatitis.[12]

    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.[9] Cases of allergic reactions to minoxidil or the non-active ingredient propylene glycol, which is found in some topical minoxidil formulations, have been reported. Pseudoacromegaly is an extremely rare side effect reported with large doses of oral minoxidil.[13]

    Minoxidil may cause hirsutism, although it is exceedingly rare and reversible by discontinuation of the drug.[14]

    Mechanism of action

    The mechanism by which minoxidil promotes hair growth is not fully understood. Minoxidil is a potassium channel opener, causing hyperpolarization of cell membranes. Hypothetically, by widening blood vessels and opening potassium channels, it allows more oxygen, blood, and nutrients to the follicles. 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. Several studies demonstrated that the activity of sulfotransferase in hair follicles predict minoxidil response in the treatment of hair loss.[15][16][17]

    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.[18] Minoxidil is also a vasodilator.[19] 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 minoxidil therapy.[20]

    History

    Initial application

    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.[21] These studies resulted in FDA approving minoxidil (with the trade name 'Loniten') in the form of oral tablets to treat high blood pressure in 1979.[22]

    Hair growth

    When Upjohn received permission from the FDA to test the new drug as medicine for hypertension they approached Charles A. Chidsey MD, Associate Professor of Medicine at the University of Colorado School of Medicine.[21] He conducted two studies,[23][24] the second study showing unexpected hair growth. Puzzled by this side-effect, Chidsey consulted Guinter Kahn and discussed the possibility of using minoxidil for treating hair loss.

    Kahn along with his colleague Paul J. Grant MD obtained a certain amount of the drug and conducted their own research, apparently without notifying Upjohn or Chidsey.[25] The two doctors had been experimenting with a 1% solution of minoxidil mixed with several alcohol-based liquids.[26] They tried to patent the drug for hair loss prevention, but found that Upjohn had already done this. A decade-long trial between Kahn and Upjohn 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.[25]

    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.[22]

    In August 1988, the FDA finally approved the drug for treating baldness in men[22][26] under the trade name 'Rogaine' (FDA rejected Upjohn's first choice, Regain, as misleading[27]). 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".[27]

    In 1991, Upjohn made the product available for women.[26]

    On February 12, 1996, the FDA approved both the over-the-counter sale of the drug and the production of generic formulations of minoxidil.[22] Upjohn replied to that by lowering prices to half the price of the prescription drug[26] and by releasing a prescription 5% formula of Rogaine in 1997.[22]

    In 1998, a 5% formulation of minoxidil was approved for nonprescription sale by the FDA.[28]

    As of 2014, it was the only topical product that is FDA-approved for androgenic hair loss.[5]

    The drug is available over the counter in many countries, including United Kingdom[4], Sweden and Germany (available from registered pharmacies only).

    Trade names

    As of June 2017 Minoxidil was marketed under many trade names worldwide: 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, 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, Moxidil, Neo-Pruristam, Neocapil, Neoxidil, Nherea, Noxidil, Oxofenil, Pilfud, Pilogro, Pilomin, Piloxidil, Recrea, Regain, Regaine, Regaxidil, Regro, Regroe, Regrou, Regrowth, Relive, Renobell Locion, Reten, Rexidil, Rogaine, Rogan, Si Bi Shen, Splendora, Superminox, Trefostil, Tricolocion, Tricoplus, Tricovivax, Tricoxane, Trugain, Tugain, Unipexil, Vaxdil, Vius, Womens Regaine, Xenogrow, Xue Rui, Ylox, and Zeldilon.[29] It was also marketed as combination drug 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.[29]

    See also

    References

    1. ↑ product, sigma. "M4145 Sigma ≥99% (TLC)". sigmaaldrich.com. sigma. Archived from the original on 2 October 2016. Retrieved 29 September 2016.
    2. ↑ cayman chemical, company. "safety data sheet" (PDF). caymanchem.com. cayman chemical company. Archived (PDF) from the original on 1 October 2016. Retrieved 29 September 2016.
    3. ↑ archives, dailymed. "loniten- minoxidil tablet". dailymed.nlm.nih.gov. dailymed. Archived from the original on 16 August 2016. Retrieved 29 September 2016.
    4. 1 2 3 "Minoxidil Regular Strength". UK Electronic Medicines Compendium. 18 August 2015. Archived from the original on 8 January 2017. Retrieved 8 January 2017.
    5. 1 2 Varothai, S; Bergfeld, WF (July 2014). "Androgenetic alopecia: an evidence-based treatment update". American Journal of Clinical Dermatology. 15 (3): 217–30. doi:10.1007/s40257-014-0077-5. PMID 24848508.
    6. ↑ Goren, A; Shapiro, J; Roberts, J; McCoy, J; Desai, N; Zarrab, Z; Pietrzak, A; Lotti, T (2015). "Clinical utility and validity of minoxidil response testing in androgenetic alopecia". Dermatologic Therapy. 28 (1): 13–6. doi:10.1111/dth.12164. PMID 25112173.
    7. ↑ Hordinsky, M; Donati, A (July 2014). "Alopecia areata: an evidence-based treatment update". American Journal of Clinical Dermatology. 15 (3): 231–46. doi:10.1007/s40257-014-0086-4. PMID 25000998.
    8. ↑ "Rogaine Side Effects in Detail - Drugs.com". drugs.com. Archived from the original on 2017-09-22.
    9. 1 2 "Minoxidil Official FDA information, side effects and uses". Drugs.com. Archived from the original on 2017-09-22.
    10. ↑ "Rogaine Side Effects in Detail - Drugs.com". drugs.com. Archived from the original on 2017-09-22.
    11. ↑ "FAQs for Men - Hair Growth Education - ROGAINE®". www.rogaine.com. Archived from the original on 2009-11-10.
    12. ↑ "Dandruff and Seborrheic Dermatitis". Medscape.com. Archived from the original on 2010-10-28. Retrieved 2009-10-09.
    13. ↑ Nguyen, K.; Marks Jr, J. (2003). "Pseudoacromegaly induced by the long-term use of minoxidil". Journal of the American Academy of Dermatology. 48 (6): 962–965. doi:10.1067/mjd.2003.325. PMID 12789195.
    14. ↑ Dawber, RP; Rundegren, J (May 2003). "Hypertrichosis in females applying minoxidil topical solution and in normal controls". Journal of the European Academy of Dermatology and Venereology. 17 (3): 271–5. PMID 12702063.
    15. ↑ Goren, A.; Shapiro, J.; Roberts, J.; McCoy, J.; Desai, N.; Zarrab, Z.; Pietrzak, A.; Lotti, T. (2015). "Clinical utility and validity of minoxidil response testing in androgenetic alopecia". Dermatologic Therapy. 28 (1): 13–6. doi:10.1111/dth.12164. PMID 25112173.
    16. ↑ Roberts, J.; Desai, N.; McCoy, J.; Goren, A. (2014). "Sulfotransferase activity in plucked hair follicles predicts response to topical minoxidil in the treatment of female androgenetic alopecia". Dermatologic Therapy. 27 (4): 252–254. doi:10.1111/dth.12130.
    17. ↑ Goren, A.; Castano, J. A.; McCoy, J.; Bermudez, F.; Lotti, T. (2014). "Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia". Dermatologic Therapy. 27 (3): 171–173. doi:10.1111/dth.12111.
    18. ↑ Scow, DT; Nolte, RS; Shaughnessy, AF (April 1999). "Medical treatments for balding in men". American Family Physician. 59 (8): 2189–94. PMID 10221304. Archived from the original on 2012-09-28.
    19. ↑ "Vasodilators". mayoclinic.com. Archived from the original on 2011-03-09.
    20. ↑ "Minoxidil Response Testing in Males With Androgenetic Alopecia - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Archived from the original on 2017-01-18.
    21. 1 2 Douglas Martin (2014-09-19). "Guinter Kahn, Inventor of Baldness Remedy, Dies at 80". The New York Times. Archived from the original on 2015-05-11. Retrieved 2015-05-11.
    22. 1 2 3 4 5 Conrad, Peter (2008). "Extension". The Medicalization of Society: On the Transformation of Human Conditions into Treatable Disorders. JHU Press. p. 37. ISBN 0801892341. Retrieved 2015-05-11. (Google Books)
    23. ↑ Gilmore, Edward; Weil, John; Chidsey, Charles (5 March 1970). "Treatment of Essential Hypertension with a New Vasodilator in Combination with Beta-Adrenergic Blockade". New England Journal of Medicine. 282 (10): 521–527. doi:10.1056/NEJM197003052821001.
    24. ↑ Gottlieb, Thomas; Katz, Fred; Chidsey, Charles (March 1972). "Combined Therapy with Vasodilator Drugs and Beta Adrenergic Blockade". Circulation. 45 (3): 571–582. doi:10.1161/01.CIR.45.3.571.
    25. 1 2 Norman M. Goldfarb (March 2006). "When Patents Became Interesting in Clinical Research" (PDF). The Journal of Clinical Research Best Practices. 2 (3). Archived from the original (PDF) on 2015-05-11. Retrieved 2015-05-11.
    26. 1 2 3 4 Will Lester (May 13, 1996). "Hair-rasing tale: no fame for men who discovered Rogaine". The Daily Gazette. Retrieved 2015-05-11.
    27. 1 2 Kuntzman, Gersh (2001). Hair!: Mankind's Historic Quest to End Baldness. Random House Publishing Group. p. 172. ISBN 0679647090. Retrieved 2015-05-11. (Google Books)
    28. ↑ Pray, Stephen W. (2006). Nonprescription Product Therapeutics. Lippincott Williams & Wilkins. p. 663. ISBN 0781734983. Retrieved 2015-05-11. (Google Books)
    29. 1 2 Drugs.com International brand names for minoxidil Archived 2017-08-08 at the Wayback Machine. Page accessed June 26, 2017
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