Minoxidil

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Minoxidil
A space filling model of the molecule.
Minoxidil-from-xtal-3D-balls.png
Clinical data
Trade namesRogaine, Loniten, others
AHFS/Drugs.comMonograph
MedlinePlusa682608
License data
Pregnancy
category
Routes of
administration		By mouth, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismPrimarily liver
Elimination half-life4.2 h
ExcretionKidney
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.048.959 Edit this at Wikidata
Chemical and physical data
FormulaC9H15N5O
Molar mass209.253 g·mol−1
3D model (JSmol)
Melting point248 °C (478 °F)
Solubility in water<1
SMILES
InChI
 ☒NcheckY (what is this?)  

Minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide), sold under the brand name Rogaine among others, is a medication used for the treatment of high blood pressure and pattern hair loss in males and females.[4][5][6] It is an antihypertensive vasodilator.[9] It is available as a generic medication by prescription in oral tablet form and over the counter as a topical liquid or foam.[7][8][10][11]

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.[12] Minoxidil must be used indefinitely for continued support of existing hair follicles and the maintenance of any experienced hair regrowth.[5][6]

Its effect in people with alopecia areata is unclear.[13]

It takes time for minoxidil to work and deliver noticeable effects. Men can go as long as 3-4 months before noticing hair regrowth with minoxidil.[14]

Side effects[]

Topically applied minoxidil is generally well tolerated, but common side effects include itching 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.[15] Other side effects may include rash, itching, difficulty breathing, 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.[15] Temporary hair loss is a common side effect of minoxidil treatment.[16] 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.[17]

Side effects of oral minoxidil may include swelling of the face and extremities, rapid heartbeat, or lightheadedness. Cardiac lesions, such as focal necrosis of the papillary muscle and subendocardial areas of the left ventricle, have been observered in laboratory animals treated with minoxidil.[18] 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.[19]

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.[20] 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.[21]

Minoxidil may cause hirsutism, although it is exceedingly rare and reversible by discontinuation of the drug.[22]

Minoxidil is suspected to be highly toxic to cats, even in small doses, as there are reported cases of cats dying shortly after coming in contact with minimal amounts of the substance.[23][24]

Mechanism of action[]

The mechanism by which minoxidil promotes hair growth is not fully understood. Minoxidil is an adenosine 5'-triphosphate-sensitive potassium channel opener,[25] 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 and A2 receptors[disambiguation needed], and that the expression of SUR2B in dermal papilla cells might play a role in the production of adenosine.[26] Minoxidil acts as an activator of the Kir6/SUR2 channel upon selective binding to SUR2.[27] 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.[28]

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.[29]

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.[30] 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.[31] 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.[32]

Minoxidil stimulates prostaglandin E2 production by activating COX-1[33] and prostaglandin endoperoxide synthase-1 but inhibites 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.[34]

Due to anti-fibrotic activity of minoxidil inhibition of enzyme lysyl hydroxylase present in fibroblast may result in 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 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.[35]

Minoxidil possesses alpha 2-adrenoceptor agonist activity,[36] 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.[37]

The minoxidil may be involved in the inhibition of serotonergic (5-HT2) receptors.[38]

Minoxidil 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.[39] Minoxidil significantly increases ROS concentration when compared to untreated cells.

In vitro Minoxidil treatment resulted in a 0.22 fold change for 5α-R2 (p < 0.0001). This antiandrogenic effect of minoxidil, shown by significant downregulation of 5α-R2 gene expression in HaCaT cells, may be one of its mechanisms of action in alopecia.[40]

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.[41] 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.[42]

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.[43] 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.[44][45]

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 MD, Associate Professor of Medicine at the University of Colorado School of Medicine.[43] He conducted two studies,[46][47] 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.

Kahn along with his colleague Paul J. Grant MD had obtained a certain amount of the drug 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.[48] The two doctors had been experimenting with a 1% solution of minoxidil mixed with several alcohol-based liquids.[49] Both parties filed patents to use the drug 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.[48]

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.[45]

In August 1988, the FDA approved the drug for treating baldness in men[45][49] under the brand name "Rogaine" (FDA rejected Upjohn's first choice, Regain, as misleading[50]). 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".[50]

In 1991, Upjohn made the product available for women.[49]

On February 12, 1996, the FDA approved both the over-the-counter sale of the medication and the production of generic formulations of minoxidil.[45] Upjohn replied to that by lowering prices to half the price of the prescription drug[49] and by releasing a prescription 5% formula of Rogaine in 1997.[45][51]

In 1998, a 5% formulation of minoxidil was approved for nonprescription sale by the FDA.[52]

The 5% aerosol foam formula was approved for medical use in the US in 2006.[53][54] The generic versions of the 5% aerosol foam formula were approved in 2017.[55][56]

In 2017, JAMA published a study of pharmacy prices in four states for 41 over-the-counter minoxidil products which were "gender-specified." The authors 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.[57]

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, Morr, 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.[58] 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.[58]

Side effects[]

Topical Minoxidil for hair growth have been reported by a small percentage of users to cause serious side effects, some of which were not reverted upon stopping the application.[59] Male users applying 5% topical application, once or twice a day, aged between 17 and 50, users reported a of any or a combination of:

  • Erectile Dysfunction
  • Loss of libido
  • Reduced semen volume
  • Reduced penile sensitivity
  • Prostatitis
  • Prostatic enlargement and congestion
  • Frequent urination
  • Heart palpitations
  • Random panic attacks
  • Brain fog
  • Fibromyalgia

More than 60,000 reported cases in FDA database[60]

See also[]

  • Kopexil, an analog of minoxidil missing the piperidine substituent
  • Pinacidil
  • Diazoxide
  • Finasteride

References[]

  1. ^ Jump up to: a b "Loniten Product Information". Therapeutic Goods Administration (TGA). Retrieved August 15, 2021.
  2. ^ http://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=3EE19DEB44A99CB3CA2577DD0001271C&agid=(PrintDetailsPublic)&actionid=1
  3. ^ https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=79914
  4. ^ Jump up to: a b "Loniten Tablets 5mg - Summary of Product Characteristics (SmPC)". (emc). November 24, 2020. Retrieved August 15, 2021.
  5. ^ Jump up to: a b c "Regaine for Men Extra Strength Scalp Foam 5% w/w Cutaneous Foam (GSL) - Summary of Product Characteristics (SmPC)". (emc). April 27, 2021. Retrieved August 15, 2021.
  6. ^ Jump up to: a b c "Regaine for Women Once a Day Scalp Foam 5% w/w Cutaneous Foam - Summary of Product Characteristics (SmPC)". (emc). October 28, 2020. Retrieved August 15, 2021.
  7. ^ Jump up to: a b "Minoxidil tablet". DailyMed. Retrieved August 15, 2021.
  8. ^ Jump up to: a b "Minoxidil aerosol, foam". DailyMed. Retrieved August 15, 2021.
  9. ^ "Vasodilators". mayoclinic.com. Archived from the original on March 9, 2011.
  10. ^ "Mens Rogaine Extra Strength Unscented- minoxidil solution". DailyMed. Retrieved August 15, 2021.
  11. ^ "Womens Rogaine Unscented- minoxidil solution". DailyMed. Retrieved August 15, 2021.
  12. ^ 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. S2CID 31245042.
  13. ^ 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. S2CID 32253.
  14. ^ "What Happens If I Stop Using Minoxidil Or Finasteride?". UPGUYS.
  15. ^ Jump up to: a b "Rogaine Side Effects in Detail". Drugs.com. Retrieved December 8, 2020.
  16. ^ "FAQs for Men - Hair Growth Education". ROGAINE. Archived from the original on November 10, 2009. Retrieved November 20, 2009.
  17. ^ "Dandruff and Seborrheic Dermatitis". Medscape.com. Archived from the original on October 28, 2010. Retrieved October 9, 2009.
  18. ^ "Minoxidil Official FDA information, side effects and uses". Drugs.com. Archived from the original on September 22, 2017.
  19. ^ Nguyen KH, Marks JG (June 2003). "Pseudoacromegaly induced by the long-term use of minoxidil". Journal of the American Academy of Dermatology. 48 (6): 962–5. doi:10.1067/mjd.2003.325. PMID 12789195.
  20. ^ Claudet, Isabelle; Cortey, Caroline; Honorat, Raphaele; Franchitto, Nicolas (January 2015). "Minoxidil Topical Solution: An Unsafe Product for Children". Pediatric Emergency Care. 31 (1): 44–46. doi:10.1097/PEC.0000000000000301. PMID 12789195. S2CID 205932483.CS1 maint: uses authors parameter (link)
  21. ^ Neumann J (December 10, 2014). "Hair loss treatment may be dangerous to kids". Reuters.
  22. ^ 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. doi:10.1046/j.1468-3083.2003.00621.x. PMID 12702063. S2CID 23329383.
  23. ^ "Minoxidil Warning". www.showcatsonline.com. Archived from the original on March 8, 2019.
  24. ^ DeClementi C, Bailey KL, Goldstein SC, Orser MS (November 2004). "Suspected toxicosis after topical administration of minoxidil in 2 cats". Journal of Veterinary Emergency and Critical Care. 14 (4): 287–292. doi:10.1111/j.1476-4431.2004.04014.x.
  25. ^ Wang T (February 2003). "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): 833–40. doi:10.1124/jpet.102.043380. PMID 12538840. S2CID 6948410.
  26. ^ Marubayashi, Azusa; Nakaya, Yutaka; Fukui, Kiyoshi; Li, Ming; Arase, Seiji (2001). "Minoxidil-Induced Hair Growth is Mediated by Adenosine in Cultured Dermal Papilla Cells: Possible Involvement of Sulfonylurea Receptor 2B as a Target of Minoxidil". Journal of Investigative Dermatology. 117 (6): 1594–1600. doi:10.1046/j.0022-202x.2001.01570.x. PMID 11886528.
  27. ^ Fukushiro-Lopes, Daniela; Hegel, Alexandra D.; Russo, Angela; Senyuk, Vitalyi; Liotta, Margaret; Beeson, Gyda C.; Beeson, Craig C.; Burdette, Joanna; Potkul, Ronald K.; Gentile, Saverio (May 8, 2020). "Repurposing Kir6/SUR2 Channel Activator Minoxidil to Arrests Growth of Gynecologic Cancers". Frontiers in Pharmacology. 11: 577. doi:10.3389/fphar.2020.00577. ISSN 1663-9812. PMC 7227431. PMID 32457608.
  28. ^ Otomo, Susumu (March 2002). "[Hair growth effect of minoxidil]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica. 119 (3): 167–174. doi:10.1254/fpj.119.167. ISSN 0015-5691. PMID 11915519.
  29. ^ Messenger, A. G.; Rundegren, J. (2004). "Minoxidil: mechanisms of action on hair growth". The British Journal of Dermatology. 150 (2): 186–194. doi:10.1111/j.1365-2133.2004.05785.x. PMID 14996087. S2CID 19308112.
  30. ^ "Effects of minoxidil on cell proliferation and intracellular glutathione status of murine (L929) fibroblasts". ResearchGate. Retrieved August 26, 2021.
  31. ^ Yum, Soohwan; Jeong, Seongkeun; Kim, Dohoon; Lee, Sunyoung; Kim, Wooseong; Yoo, Jin-Wook; Kim, Jung-Ae; Kwon, Oh Sang; Kim, Dae-Duk; Min, Do Sik; Jung, Yunjin (December 25, 2017). "Minoxidil Induction of VEGF Is Mediated by Inhibition of HIF-Prolyl Hydroxylase". International Journal of Molecular Sciences. 19 (1): 53. doi:10.3390/ijms19010053. ISSN 1422-0067. PMC 5796003. PMID 29295567.
  32. ^ [1], "Blocking utilization of tetrahydrobiopterin to block induction of nitric oxide synthesis", issued 1995-12-19 
  33. ^ Hwang, Ji-Hye; Chu, Howard; Ahn, Yuri; Kim, Jino; Kim, Do-Young (2019). "HMGB1 promotes hair growth via the modulation of prostaglandin metabolism". Scientific Reports. 9 (1): 6660. Bibcode:2019NatSR...9.6660H. doi:10.1038/s41598-019-43242-2. PMC 6491442. PMID 31040377.
  34. ^ Suchonwanit P, Thammarucha S, Leerunyakul K (2019). "Minoxidil and its use in hair disorders: a review". Drug Design, Development and Therapy. 13: 2777–2786. doi:10.2147/DDDT.S214907. PMC 6691938. PMID 31496654.
  35. ^ Kassai, B.; Bouyé, P.; Gilbert-Dussardier, B.; Godart, F.; Thambo, J. B.; Rossi, M.; Cochat, P.; Chirossel, P.; Luong, S.; Serusclat, A.; Canterino, I.; Mercier, C.; Rabilloud, M.; Pivot, C.; Pirot, F.; Ginhoux, T.; Coopman, S.; Grenet, G.; Gueyffier, F.; Di-Fillippo, S.; Bertholet-Thomas, A. (2019). "Minoxidil versus placebo in the treatment of arterial wall hypertrophy in children with Williams Beuren Syndrome". BMC Pediatrics. 19 (1): 170. doi:10.1186/s12887-019-1544-1. PMC 6537216. PMID 31138170. CC-BY icon.svg Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
  36. ^ Sharma, N.; Mehta, A. A.; Santani, D. D.; Goyal, R. K. (1997). "Evidence for alpha 2-adrenoceptor agonist activity of minoxidil". The Journal of Pharmacy and Pharmacology. 49 (9): 935–937. doi:10.1111/j.2042-7158.1997.tb06139.x. PMID 9306265. S2CID 84233773.
  37. ^ "Minoxidil: An Underused Vasodilator for Resistant or Severe Hypertension".
  38. ^ Wasiński, R.; Godlewski, G.; Wróbel, B.; Buckzko, W. (May 1995). "Interactions of minoxidil with vasoconstrictive agents in isolated rat tail artery". Acta Poloniae Pharmaceutica. 52 (3): 253–256. ISSN 0001-6837. PMID 8960256.
  39. ^ Gu, Yan-ting; Xue, Yi-xue; Wang, Yan-feng; Wang, Jin-hui; Chen, Xia; ShangGuan, Qian-ru; Lian, Yan; Zhong, Lei; Meng, Ying-nan (December 2013). "Minoxidil sulfate induced the increase in blood-brain tumor barrier permeability through ROS/RhoA/PI3K/PKB signaling pathway". Neuropharmacology. 75: 407–415. doi:10.1016/j.neuropharm.2013.08.004. ISSN 1873-7064. PMID 23973310. S2CID 20676988.
  40. ^ Pekmezci, Erkin; Türkoğlu, Murat (December 2017). "Minoxidil Acts as an Antiandrogen: A Study of 5α-reductase Type 2 Gene Expression in a Human Keratinocyte Cell Line". Acta Dermatovenerologica Croatica: ADC. 25 (4): 271–275. ISSN 1847-6538. PMID 30064598.
  41. ^ Scow DT, Nolte RS, Shaughnessy AF (April 1999). "Medical treatments for balding in men". American Family Physician. 59 (8): 2189–94, 2196. PMID 10221304. Archived from the original on September 28, 2012.
  42. ^ Clinical trial number NCT02198261 for "Minoxidil Response Testing in Males With Androgenetic Alopecia" at ClinicalTrials.gov
  43. ^ Jump up to: a b Douglas Martin (September 19, 2014). "Guinter Kahn, Inventor of Baldness Remedy, Dies at 80". The New York Times. Archived from the original on November 5, 2014. Retrieved May 11, 2015.
  44. ^ "Loniten: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved August 15, 2021.
  45. ^ Jump up to: a b c d e Conrad P (2008). "Extension". The Medicalization of Society: On the Transformation of Human Conditions into Treatable Disorders. JHU Press. p. 37. ISBN 978-0801892349. Retrieved May 11, 2015. (Google Books)
  46. ^ Gilmore E, Weil J, Chidsey C (March 1970). "Treatment of essential hypertension with a new vasodilator in combination with beta-adrenergic blockade". The New England Journal of Medicine. 282 (10): 521–7. doi:10.1056/NEJM197003052821001. PMID 4391708.
  47. ^ Gottlieb TB, Katz FH, Chidsey CA (March 1972). "Combined therapy with vasodilator drugs and beta-adrenergic blockade in hypertension. A comparative study of minoxidil and hydralazine". Circulation. 45 (3): 571–82. doi:10.1161/01.CIR.45.3.571. PMID 4401051.
  48. ^ Jump up to: a b 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 May 18, 2015. Retrieved May 11, 2015.
  49. ^ Jump up to: a b c d Will Lester (May 13, 1996). "Hair-rasing tale: no fame for men who discovered Rogaine". The Daily Gazette. Retrieved May 11, 2015.
  50. ^ Jump up to: a b Kuntzman G (2001). Hair!: Mankind's Historic Quest to End Baldness. Random House Publishing Group. p. 172. ISBN 978-0679647096. Retrieved May 11, 2015. (Google Books)
  51. ^ "Drug Approval Package: Rogaine NDA# 020834". U.S. Food and Drug Administration (FDA). August 8, 2003. Retrieved August 15, 2021.
  52. ^ Pray SW (2006). Nonprescription Product Therapeutics. Lippincott Williams & Wilkins. p. 663. ISBN 978-0781734981. Retrieved May 11, 2015. (Google Books)
  53. ^ "Drug Approval Package: Men's Rogaine (5% Minoxidil) NDA #021812". U.S. Food and Drug Administration (FDA). May 6, 2008. Retrieved August 15, 2021.
  54. ^ "Rogaine: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved August 15, 2021.
  55. ^ "Minoxidil: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved August 15, 2021.
  56. ^ "CDER 2017 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). February 20, 2018. Retrieved August 15, 2021.
  57. ^ Wehner MR, Nead KT, Lipoff JB (August 2017). "Association Between Gender and Drug Cost for Over-the-Counter Minoxidil". JAMA Dermatology. 153 (8): 825–826. doi:10.1001/jamadermatol.2017.1394. PMC 5817599. PMID 28593214.
  58. ^ Jump up to: a b Drugs.com International brand names for minoxidil Archived August 8, 2017, at the Wayback Machine Page accessed June 26, 2017
  59. ^ Wu M, Yu Q, Li Q (December 2016). "Differences in reproductive toxicology between alopecia drugs: an analysis on adverse events among female and male cases". Oncotarget. 7 (50): 82074–82084. doi:10.18632/oncotarget.12617. PMC 5347675. PMID 27738338.
  60. ^ "Qlik Sense". fis.fda.gov. Retrieved April 7, 2021.

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