Minoxidil

Structural formula
General
Non-proprietary name	Minoxidil
other names	2,6-diamino-4-piperidinopyrimidine-1-oxide 6-piperidinopyrimidine-2,4-diamine-3-oxide
Molecular formula	C 9 H 15 N 5 O
Brief description	white to almost white, crystalline powder
External identifiers / databases
CAS number 38304-91-5 EC number 253-874-2 ECHA InfoCard 100,048,959 PubChem 4201 DrugBank DB00350 Wikidata Q424165
Drug information
ATC code	C02 DC01 , D11 AX01
Drug class	Antihypertensive drugs
Mechanism of action	direct attack on the smooth muscles of small arteries
properties
Molar mass	209.25 g mol −1
Physical state	firmly
Melting point	248 ° C
pK s value	4.61
solubility	sparingly soluble in water (2200 mg l −1 ) Easily soluble in methanol and propylene glycol
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 302-315-319-335 P: 261-305 + 351 + 338
Toxicological data	1321 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Minoxidil is a drug used as an antihypertensive agent and to treat hereditary hair loss ( androgenetic alopecia ).

Chemically it is a derivative ( derivative ) of the pyrimidine kopexil .

history

Minoxidil was originally developed as an oral drug for the treatment of high blood pressure in the United States in the 1970s . In 1982 it came onto the German market under the name Lonolox®. Kaushik D. Meisheri was only able to explain the exact mechanism of action of minoxidil or the active metabolite minoxidil sulfate six years later. Minoxidil is a potassium channel opener and thus leads to hyperpolarization in cells. The resulting widened blood vessels presumably ensure a better supply of nutrients to the hair follicles and thus help to lengthen the growth phases of the hair. Increased hair growth was found to be a side effect of the application. The Upjohn company then sponsored specific studies on how minoxidil can combat hair loss and developed a 2% topical minoxidil solution with the trade name Regaine (in most countries) or Rogaine (USA, Canada, Scandinavia) for the treatment of congenital baldness.

Today, Minoxidil is sold as a 5% solution or as a 5% foam for men and as a 2% solution for women for the treatment of hereditary baldness. As a medication against high blood pressure, Minoxidil is available in tablet form with a strength of 2.5 mg and 10 mg.

Clinical information

Application areas (indications)

high blood pressure

Minoxidil is a reserve drug for otherwise therapy-resistant high blood pressure . Therapy-resistant high blood pressure is used when maximum therapeutic doses of other antihypertensive agents in triple combination using a diuretic have not shown sufficient success.

Hair loss

In men aged 18 to 49 years, minoxidil can stabilize the course of congenital baldness (alopecia) for scalp surfaces with a diameter of 3–10 cm. Its effectiveness in the temples (" receding hairline ") has not been clinically proven .

According to the manufacturer, hair loss is stopped in 70% to 80% of cases. Hair regrowth occurs in up to 30%. However, a satisfactory result is achieved with less than 10%. The best results are expected for dark-haired people under the age of 50 who have had hair loss less than 10 years ago.

In women, minoxidil can stabilize the course of a diffuse thinning of the scalp caused by the condition in the crown area and counteract the progression of baldness.

Type and duration of application

high blood pressure

Minoxidil is taken orally. The dose is gradually increased until the desired decrease in blood pressure is achieved or the maximum permitted dose is reached. There are no restrictions on the duration of use. Minoxidil causes edema (water retention) and reflex tachycardia, so Minoxidil should always be given at the same time as a diuretic and a beta blocker .

Hair loss

The drug is applied to the scalp as a solution or foam 2 times a day. In the event of success (approx. 30% of the male test subjects), the first results are noticeable after three to four months. The maximum effectiveness is reached after about 12 months. When stopped, the hair loss will progress again after three to four months. In some patients, temporary increased hair loss was observed two to six weeks after the start of treatment, which can result from newly growing hair pushing the "old" no longer active hair out of the scalp. This effect is called the "shedding effect".

Contraindications (contraindications)

Minoxidil must not be taken if:

• Hypersensitivity to the active ingredient
• Pulmonary hypertension due to mitral stenosis
• Pheochromocytoma

Minoxidil for use on the scalp must not be used in:

• concomitant use of other topical drugs on the scalp
• sudden or uneven hair loss
• Pregnancy and breastfeeding mothers
• Occasional indications of cosmetically disturbing reversible hair growth on the face during the treatment (applies to women using the solution or the foam for men)
• Use on the hairline (forehead, temples) (applies to the use of men's foam)
• lack of family evidence of premature hair loss or thinning of scalp hair

Drug interactions

high blood pressure

The simultaneous administration of alpha blockers can lead to severe orthostatic reactions. Some neuroleptics also increase the effect of minoxidil.

Hair loss

There is currently no evidence of interactions with other agents. Theoretically, there is a possibility that minoxidil may increase orthostatic hypotension (drop in blood pressure when changing from lying down to standing) in patients concomitantly taking peripheral vasodilator drugs to lower blood pressure. This has not yet been clinically verified.

Adverse effects (side effects)

high blood pressure

Side effects include increased sodium and water retention , hyperglycaemia , hyperuricaemia , increased heart rate, and hypertrichosis .

Hair loss

Due to the fact that stronger hair grows out of the same follicles, hair loss often occurs during treatment. In individual cases, this occurs more intensely after four to six weeks during treatment and is also reported after minoxidil has been discontinued.

The following can also occur:

Common (may affect up to 1 in 10 people):

• a headache
• Itching, reddening of the skin, hypertrichosis
• Increased hair growth outside the hairy head
• hypertension

Not known (frequency cannot be estimated from the available data):

• Hypersensitivity reactions and angioedema with reactions such as B. swelling of the face, lips, tongue and / or oropharynx, more general

Itching, general rash, tightness in the throat.

Minoxidil is highly toxic to cats and accidental skin contact can be fatal for them.

Mechanism of action (pharmacodynamics)

Minoxidil is a potassium channel opener of cellular potassium channels that contains nitric oxide (NO), a vasodilator , in its chemical structure and possibly acts as a NO agonist . This mechanism of action hyperpolarizes the smooth muscles of the arterial vessels . This is followed by direct relaxation (slackening) of the arterioles (small arteries) and thus a drop in blood pressure.

When applied topically , minoxidil can stop androgenetic hair loss in the early to middle stages. The mode of action has not yet been clarified, it is assumed that Minoxidil expands the capillaries due to its antihypertensive effect and thus promotes blood circulation. In addition, minoxidil can stop hair loss by shortening the resting phase (telogen phase) of the hair cycle. As a result, the growth phase (anagen phase) is reached faster and the growth of new hair is stimulated.

Chemical and pharmaceutical information

Minoxidil is synthesized from barbituric acid in several stages.

Barbituric acid is first reacted with phosphorus oxychloride to form 2,4,6-trichloropyrimidine; this then with ammonia : the reaction product is reacted with potassium 2,4-dichlorophenolate. Oxidation with meta-chloroperbenzoic acid then takes place . Finally, the phenolate is nucleophilically exchanged for piperidine .

Trade names

• To lower blood pressure ( perorally ): Loniten (A, CH), Lonolox (D)
• Against hair loss ( topical ): Alopexy (D, A, CH), Neocapil (CH), Regaine (D, A, CH), Rogaine (USA)

Web links

• Clinical Research Center for Hair and Skin Science (CRC) at the Clinic for Dermatology, Venereology and Allergology on Campus Charité Mitte: "Androgenetic alopecia in men (predisposed hair loss)"

Individual evidence

1. ↑ ^{a b} European Pharmacopoeia Commission (Ed.): European Pharmacopoeia 5th Edition . tape 5.0-5.8 , 2006.
2. ^ Ruß, Endres, Arzneimittelpocket Plus 2008, 4th edition Oct. 2007, ISBN 978-3-89862-287-5 .
3. ↑ ^{a b c d} Entry on minoxidil in the ChemIDplus database of the United States National Library of Medicine (NLM), accessed on June 16, 2017.
4. ↑ ^{a b} Minoxidil data sheet from Sigma-Aldrich , accessed on June 16, 2017 ( PDF ).
5. ^ Wolf-Dieter Müller-Jahncke , Christoph Friedrich , Ulrich Meyer: Medicinal history . 2., revised. and exp. Ed. Wiss. Verl.-Ges, Stuttgart 2005, ISBN 3-8047-2113-3 , p. 166 .
6. ^ New York Times: Hair Growth Drug Seen as a Wonder for Upjohn , May 28, 1985 (accessed November 24, 2014).
7. ↑ Red List online, accessed December 4, 2014.
8. ^ ^{A b} Pfizer Pharma GmbH: Specialist information Lonolox. Status: October 2008.
9. ^ ^{A b c d e f} Johnson & Johnson GmbH: Specialist information Regaine men. Status: August 2014.
10. ^ ^{A b c d e} Johnson & Johnson GmbH: Specialist information Regaine women. Status: August 2014.
11. ^ Rogaine Side Effects
12. ↑ Minoxidil Official FDA information, side effects and uses . Drugs.com.
13. ↑ Kidwai BJ, George M. Hair loss with minoxidil withdrawal. Lancet. 1992; 340: 609-610. PMID 1355180 .
14. ↑ Camille DeClementi, Keith L. Bailey, Spencer C. Goldstein, and Michael Scott Orser: Suspected toxicosis after topical administration of minoxidil in 2 cats . In: Journal of Veterinary Emergency and Critical Care . 14, No. 4, December 2004, pp. 287-292. doi : 10.1111 / j.1476-4431.2004.04014.x .
15. ^ Minoxidil Warning . ShowCatsOnline.com. Retrieved January 18, 2007: "Very small amounts of Minoxidil can result [in] serious problems or death"
16. ^ Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dietmar Reichert: Pharmaceutical Substances, 4th edition (2000), 2 volumes published by Thieme-Verlag Stuttgart, ISBN 978-1-58890-031-9 ; online since 2003 with biannual additions and updates.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !