Minoxidil

Minoxidil
A space filling model of the molecule.
Clinical data
Trade names Rogaine
AHFS/Drugs.com Monograph
Pregnancy
category
  • C
Routes of
administration		 Oral / topical
ATC code C02DC01 (WHO) D11AX01 (WHO)
Legal status
Legal status
  • P(UK) for topical use, otherwise POM. Cannot be prescribed on the NHS.
Pharmacokinetic data
Metabolism Primarily hepatic
Biological half-life 4.2 h
Excretion renal
Identifiers
CAS Number 38304-91-5 YesY
PubChem (CID) 4201
IUPHAR/BPS 4254
DrugBank DB00350 N
ChemSpider 10438564 YesY
UNII 5965120SH1 N
KEGG D00418 N
ChEBI CHEBI:6942 N
ChEMBL CHEMBL802 N
PDB ligand ID MXD (PDBe, RCSB PDB)
ECHA InfoCard 100.048.959
Chemical and physical data
Formula C9H15N5O
Molar mass 209.251 g/mol
3D model (Jmol) Interactive image
Melting point 248 °C (478 °F)
Solubility in water <1 mg/mL (20 °C)
 NYesY (what is this?)  (verify)

Minoxidil is an antihypertensive vasodilator medication. It also slows hair loss and promotes hair regrowth in some people. Now off-patent, it is available over the counter for the treatment of androgenic alopecia.

Medical uses

Minoxidil, applied topically, is widely used for the treatment of hair loss. It is effective in helping promote hair growth in both men and women with androgenic alopecia.[4] About 40% of men experience hair regrowth after 3–6 months.[5] Minoxidil must be used indefinitely for continued support of existing hair follicles and the maintenance of any experienced hair regrowth.[6][7] It is the only topical product that is FDA-approved for androgenic hair loss.[4] Treatments usually include a 5% concentration solution that is designed for men, and a 2% concentration solution for women.[8] Minoxidil has been approved for female use by the FDA.[9]

The drug is available over the counter in the United Kingdom.[10]

Its effect in people with alopecia areata is unclear.[11]

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, as well as unwanted hair growth elsewhere on the body. Exacerbation of hair loss/alopecia has been reported.[12][13] 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.[14] Temporary hair loss is a common side effect of minoxidil treatment.[15] 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.[16] Some formulations of minoxidil substitute lipid nanosomes in order to reduce contact dermatitis from the alcohol and propylene glycol vehicle.[17][18]

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.[13] 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.[19]

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 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 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.[20][21][22]

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.[23] Minoxidil is also a vasodilator.[24] 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.[25]

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.[26] 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.[27]

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.,[26] who conducted two studies,[28][29] 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.[30] The two doctors had been experimenting with a 1% solution of minoxidil mixed with several alcohol-based liquids.[31] 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.[30]

Meantime the effect of minoxidil on hair loss prevention was so clear that in the 80's physicians were prescribing Loniten off-label to their balding patients.[27]

In August 18, 1988 the FDA finally approved the drug for treating baldness in men[27][31] under the trade name 'Rogaine' (FDA rejected Upjohn's first choice, Regain, as misleading[32]). The agency concluded that although "the product will not work for everyone", 39 percent of the men studied had "moderate to dense hair growth on the crown of the head".[32]

In 1991 Upjohn made the product available for women.[31]

On February 12, 1996 FDA approved both the over-the-counter sale of the drug and the production of generic formulations of minoxidil.[27] Upjohn replied to that by lowering prices to half the price of the prescription drug[31] and by releasing a prescription 5% formula of Rogaine in 1997.[27]

In 1998 a 5% formulation of minoxidil was approved for nonprescription sale by the FDA.[33]

Application

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.[34] 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.[35] Therefore, when treatment is stopped, the DHT has its expected effect of shrinking and ultimately destroying the genetically predisposed hair follicles. There are multiple types of minoxidil applications: dropper, foam and spray.

Trade names

Minoxidil is marketed under many trade names worldwide.[36]

See also

References

  1. ↑ product, sigma. "M4145 Sigma ≥99% (TLC)". sigmaaldrich.com. sigma. Retrieved 29 September 2016.
  2. ↑ cayman chemical, company. "safety data sheet" (PDF). caymanchem.com. cayman chemical company. Retrieved 29 September 2016.
  3. ↑ archives, dailymed. "loniten- minoxidil tablet". dailymed.nlm.nih.gov. dailymed. Retrieved 29 September 2016.
  4. 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.
  5. ↑ "Clinical utility and validity of minoxidil response testing in androgenetic alopecia.". Dermatol Ther. 28 (1): 13–6. doi:10.1111/dth.12164. PMID 25112173.
  6. ↑ Olsen, Elise A.; Dunlap, Frank E.; Funicella, Toni; Koperski, Judith A.; Swinehart, James M.; Tschen, Eduardo H.; Trancik, Ronald J. (2002). "A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men". Journal of the American Academy of Dermatology. 47 (3): 377–385. doi:10.1067/mjd.2002.124088. ISSN 0190-9622.
  7. ↑ Olsen, Elise A.; Weiner, Madeline S.; Amara, Ingrid A.; DeLong, Elizabeth R. (1990). "Five-year follow-up of men with androgenetic alopecia treated with topical minoxidil". Journal of the American Academy of Dermatology. 22 (4): 643–646. doi:10.1016/0190-9622(90)70089-Z. ISSN 0190-9622.
  8. ↑ "Grant v. Pharmacia & Upjohn Co.". Retrieved 2009-01-17.
  9. ↑ "Drugs@FDA: FDA Approved Drug Products". www.accessdata.fda.gov. Retrieved 2016-04-30.
  10. ↑ Drug Tariff, 2009/04/11
  11. ↑ 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.
  12. ↑ http://www.drugs.com/sfx/rogaine-side-effects.html
  13. 1 2 "Minoxidil Official FDA information, side effects and uses". Drugs.com.
  14. ↑ Rogaine Side Effects | Drugs.com
  15. ↑ FAQs | Rogaine
  16. ↑ "Dandruff and Seborrheic Dermatitis". Medscape.com. Retrieved 2009-10-09.
  17. ↑ Balakrishnan P, Shanmugam S, Lee WS, Lee WM, Kim JO, Oh DH, Kim DD, Kim JS, Yoo BK, Choi HG, Woo JS, Yong CS (1 February 2009). "Formulation and in vitro assessment of minoxidil Nanosomes for enhanced skin delivery". International Journal of Phermaceutics. 377 (1-2): 1–8. doi:10.1016/j.ijpharm.2009.04.020. PMID 19394413.
  18. ↑ Padois K, Cantiéni C, Bertholle V, Bardel C, Pirot F, Falson F (16 June 2011). "Solid lipid nanoparticles suspension versus commercial solutions for dermal delivery of minoxidil". International Journal of Pharmaceutics. 416 (1): 300–304. doi:10.1016/j.ijpharm.2011.06.014. PMID 21704140.
  19. ↑ 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.
  20. ↑ 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: 13–6. doi:10.1111/dth.12164. PMID 25112173.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ Scow, DT; Nolte, RS; Shaughnessy, AF (April 1999). "Medical treatments for balding in men". Am Fam Physician. 59 (8): 2189–94. PMID 10221304.
  24. ↑ Vasodilators | MayoClinic.com
  25. ↑ Minoxidil Response Testing in Males With Androgenetic Alopecia
  26. 1 2 Douglas Martin (2014-09-19). "Guinter Kahn, Inventor of Baldness Remedy, Dies at 80". http://www.nytimes.com/. The New York Times. Archived from the original on 2015-05-11. Retrieved 2015-05-11. External link in |website= (help)
  27. 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)
  28. ↑ Gilmore, Edward; Weil, John; Chidsey, Charles (March 5, 1970). "Treatment of Essential Hypertension with a New Vasodilator in Combination with Beta-Adrenergic Blockade". The New England Journal of Medicine, 10. Massachusetts Medical Society. 282: 521–527. doi:10.1056/NEJM197003052821001. Archived from the original on 2015-05-11. Retrieved 2015-05-11.
  29. ↑ Gottlieb, Thomas; Katz, Fred; Chidsey, Charles (March 1972). "Combined Therapy with Vasodilator Drugs and Beta Adrenergic Blockade". Circulation. Lippincott Williams & Wilkins. XLV: 571–582. doi:10.1161/01.CIR.45.3.571. Archived from the original (PDF) on 2015-05-11. Retrieved 2015-05-11.
  30. 1 2 Norman M. Goldfarb. "When Patents Became Interesting in Clinical Research". The Journal of Clinical Research Best Practices, Vol. 2, No. 3, March 2006. Archived from the original (PDF) on 2015-05-11. Retrieved 2015-05-11.
  31. 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.
  32. 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)
  33. ↑ Pray, Stephen W. (2006). Nonprescription Product Therapeutics. Lippincott Williams & Wilkins. p. 663. ISBN 0781734983. Retrieved 2015-05-11. (Google Books)
  34. ↑ minoxidil (Rogaine) - drug class, medical uses, medication side effects, and drug interactions by MedicineNet.com
  35. ↑ American Hair Loss Association | Men's Hair Loss | Causes of Hair Loss
  36. ↑ Drugs.com International brand names for minoxidil Page accessed April 8, 2016
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