Wednesday, April 20, 2011

Minoxidil: mechanisms of action on hair growth

For nearly 30 years is known that minoxidil stimulates hair growth, yet the mechanism of action of this agent is not fully understood. In animal studies it was found that minoxidil shortens telogen phase, causing premature transition of resting hair follicles into anagen. It is very likely in humans minoxidil have the same mechanism.

Administered orally, minoxidil lowers blood pressure by relaxing the smooth muscle, it is believed that this pharmacological effect is due to minoxidil sulfate - a metabolite of minoxidil, which leads to the opening-up of ATP-dependent sarkolemni potassium channels. There are several reports which suggest that the incentive effect of minoxidil on hair growth is due to the opening of potassium channels of that metabolite, but no evidence that such channels are expressed in the hair follicle. A number of in vivo effects of minoxidil are described in monocultures of several skin and follicular cell lines: stimulation of cell proliferation, inhibition of collagen synthesis, stimulation of the synthesis of vascular endothelial growth factor and prostaglandins. Some of the described effects may be important for hair growth, but it is unclear how these results could be applied in the complex biology of the hair follicle. This article will describe what information has medicine on the mode of action of minoxidil on hair growth.

Minoxidil enter service in 70 years of 20 century as a medicine for hypertension. Even then found that one of the most common side effects of taking minoxidil tablets hypertrichosis. In bald men were seen re growing in fallen hair. All this led to the creation of minoxidil topical form for treatment of androgenetic alopecia in men, and later in women. 2% howl product against hair loss occurs in the U.S. market in 1986 and in 1993 appeared and 5-percent solution.

Despite 20 years intensive research, medicine has limited data exactly how minoxidil stimulates hair growth. By contrast, the establishment of the exact mechanism of action of the preparation is of utmost importance - in terms of creating more effective therapeutic approaches to hair loss and in terms of clarifying the biology of the hair follicle.

There are several mechanisms by which the drug stimulates hair growth. Minoxidil accelerates hair growth, increases the diameter of the hair affect the hair cycle shortened telogen and prolonging anagen phase. Probably integrated action include all these mechanisms. Available data suggest that minoxidil acts mainly through the influence of the hair cycle, perhaps increasing the diameter of the hair.

Animal studies

Mori and Uno studied the effects of topical minoxidil on spontaneous hair cycle in rats. No effect was found for the length of the anagen phase, but at the expense of this telogen phase was shortened: its duration during the third cycle in untreated animals was 20 days and in treated follicles had entered anagen phase only after 1-2 telogen. The same shortening of the telogen phase was observed and the fourth cycle.

The effect of minoxidil has been studied thoroughly in macaques - mammals who develop alopecia like humans. Topical minoxidil prevented the development of skalpovo baldness and stimulate re-growth of hair in balding individuals. Histological studies found that minoxidil causes increase in the number of follicles into anagen phase and reducing those in the telogen phase. Been established and enlargement of the hair follicle.

Studies in humans

Extremely little is known about the effects of minoxidil on hair growth in humans, such studies are limited mainly to the observed response to androgenic alopecia applications topical minoxidil. In male pattern baldness (male androgenetic alopecia), a gradual reduction in the duration of anagen and longer latent period of the hair follicle (the period between the loss of telogen hair and the beginning of the next anagen). Hair follicles shrink.

Clinical trials with topical minoxidil in male and female hair loss show extremely rapid acceleration of hair growth, which becomes apparent within 6-8 months after starting therapy. The peak is usually reached in weeks 12-16. Most likely, minoxidil affects hair follicles in telogen and latency induced transition into anagen. Hypertrichosis observed in oral administration may affect the forehead and limbs. Extended hairs of these sites indicate that minoxidil also extended the duration of the anagen phase in man.

Histological studies in man are less definitive than in macaques. Abel and colleagues found a trend towards increasing otnoshtenieto anagen / telogen after 12 months of treatment with minoxidil in the bald men, but the biggest change was an increase in the average diameter of hair ". This change was most evident at 4 months, and at 12 months was observed reduction in mean diameter - probably due to the passage of small arms in the anagen hair follicle.

Minoxidil sulphate opens potassium channels

Minoxidil sulfate is one of a number of chemically unrelated drugs that cause opening plazmomembranni ATP-sensitive potassium channels. Relaxing effect of minoxidil on smooth muscle is due to precisely this mechanism. K ATP are located in many tissues and cell types - cardiomyocytes, pancreas, vascular galdka muscle, central nervous system. Several reports of clinical observations, animal studies and in vitro experiments suggest that the incentive effect of minoxidil on hair growth is related in some way with the opening K.atf effect of the preparation.

In vivo studies
Furthermore, minoxidil, opening potassium channels preparations diazoxide and pinacidil also cause hypertrichosis in humans. Bulgarian and colleagues studied the effect of topical minoxidil and three other preparation that open channels on K.atf skalpoviya hair "growing on bald monkeys. Minoxidil, cromakalin and P-1075 (analogue of pinacidil) stimulated hair growth within 20-week treatment course. Fourth oupanar of potassium channels - RP-49, 356, was not effective.

Regardless of the mechanism by which minoxidil modulate hair growth, there should be a primary effect on cellular function. Hair follicle is a complex structure consisting of epithelial, dermal, pigments and immune cells, as well as perifolikularna vascular and nervous system. Regulation of epithelial growth and differentiation and the hair cycle is based on the above structures. Many of these cells were used in studies with isolated monoxidil, but so far attempts to lokalizarane connections between minoxidil (and metabolites) and some of these cells were unsuccessful. Studies in mice have shown that minoxidil and minoxidil sulfate were concentrated in melanocytes and pigmented epithelial cells in suprapapilarniya region of the follicle. Most likely this is due to nonspecific binding to melanin.

Why minoxidil important? Although the benefits of androgenetic alopecia has been demonstrated in numerous clinical trials tend to disparage the preparation, which remains the only topical medication proven efficacy, and the only drug for hair loss in women approved. Minoxidil affects hair cycle, causing premature termination of the telogen and perhaps extend the anagen phase. Clarifying the mechanisms by which minoxidil has its effects will not only lead to more effective treatment of hair loss, but will also improve our knowledge on mechanisms controlling the hair cycle.


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