Minoxidil belongs to the class of treatment called “Potassium Channel Openers” that was used in high-blood pressure treatment. Originally introduced in the 70’s as treatment for hypertension, Minoxidil became the only approved drug from the “Potassium Channel Openers” category for use in human despite the number of drugs researched from this class.

Medication of Minoxidil resulted in some undesirable hair growth for its side effect. This observation led to the development of topical formulation of Minoxidil in treating pattern baldness in men and later on in women. Today, two types of Minoxidil appear in the market, each treating different conditions. One type is Oral Minoxidil that treats high blood pressure, while the topical solution form of Minoxidil is used as a treatment for hair-loss and baldness. The US market has first seen 2% topical Minoxidil in 1986 as hair-grower and the 5% became available in 1993.

Response of the Hair Follicle To Minoxidil

Drugs are known to stimulate hair growth in many ways. Some drugs increase the linear growth rate of hair, other may increase the diameter of the hair fiber, some may alter the hair cycle – by shortening the telogen or prolonging the anagen, and certain drugs containing Minoxidil may cause the hair follicles to respond differently with the combination of these effects. The function of Minoxidil in stimulating hair growth has already been established, but the knowledge on the working mechanism of Minoxidil is bounded.

Topical Minoxidil shortens telogen thus causing premature entry of resting hair follicles into anagen in the result of the extensive animal studies conducted on stump-tailed macaque to determine the effects of Minoxidil in the hair growth. Histological inspection on these primates showed that Minoxidil treatment causes proportional increase in anagen follicles, a decrease in the telogen follicles, and an increase in the size of the hair follicle. However, the only noted effect of Minoxidil treatment in humans is its role in the human hair cycle although the possibility of Minoxidil increasing the hair diameter is still studied.

Understanding how Minoxidil works can help many through the development of more effective treatments for hair loss disorders as much as it can help science in unraveling the biology of hair growth.

How Does Minoxidil Work?

In animal studies, Minoxidil does not stimulate the secretion of testosterone or adrenal androgen secretion; thus, it does not have any anti-androgen effects. There was no noted change in the testosterone levels after Minoxidil was administered on humans.

It was so thought that Minoxidil acts on the system by increasing the amount of blood present in the hair follicle since Minoxidil was originally used to treat high blood pressures. However, vasodilation or the dilation of the blood vessels is not noticed on other Potassium Channel Openers including Minoxidil thus the association with vasodilation in hair growth is rejected. A component of Minoxidil, the Minoxidil sulfate, was observed to be the active metabolite responsible for stimulation hair growth. When Minoxidil is taken orally, it relaxes the vascular smooth muscle by the action of the sulphated metabolite– the Minoxidil sulphate - in its component as an opener of the sarcolemnal KATP channels, thus lowering the blood pressure. Subsequent studies on the whisker follicles and on the stump-tail macaque showed that the stimulatory effect of Minoxidil on hair growth is also due to the opening of potassium channels by Minoxidil sulphate. This idea remains unproven, as to date KATP channels expressing in the hair follicles are difficult to demonstrate.

Prolongation of keratinocyte growth and an increase in the proportion of hairs in anagen in monkey and humans exhibiting pattern baldness are but some of the well-recognized effects of Minoxidil. There were also other experiments conducted, resulting in support of Minoxidil’s role in the prolongation of the survival time of keratinocytes in vitro.

The Cellular Response to Minoxidil

The unknown mechanism that allows Minoxidil to modulate hair growth affects cellular function. The hair follicle has a complex structure that is made up of epithelial, dermal, pigment and immune cells, a perifollicular vasculature and neural network. The interactions between the cells are involved in the regulation of the hair cycle and the epithelial growth and differentiation. Many studies had been done to isolate several of these cells to be able to study the Minoxidil action but until now, researches have been unsuccessful in locating the Minoxidil metabolite that binds to a specific cell population within the hair follicle.

In monocultures of the various skin and fair follicle types, there were quite a number of in vitro effects of Minoxidil which includes stimulation of cell proliferation, inhibition of collagen synthesis, stimulation of vascular enfothelial growth factor, and prostaglandin synthesis. Some or all of these effects may eventually lead to the solution of the hair-growth problem.

All the results show that Minoxidil increase vascular endothelial growth factor (VEGF) in cultured dermal papilla cell extracts. VEGF is associated with blood vessel formation and is usually strongly expressed in anagen dermal papilla in the presence of a highly vascular network, and a decreased in telogen when these blood vessels are absent. Thus, some authors theorized that Minoxidil could play a key role in the regulation of the dermal papilla vascularization.