The effect of Minoxidil on hair

Description

Minoxidil is a piperidine-pyrimidine derivative with the chemical formula C9H15N5O. The chemical name is 2, 6- diamino- 4- piperidinopyrimidine- 1- oxide. This drug is a medication that increases new hair growth in cases of hereditary hair loss. In the 1970s, Minoxidil was first introduced as an oral medication for the treatment of severe and recalcitrant hypertension. Nowadays, this drug is the only US FDA-approved topical drug for the treatment of androgenetic alopecia (AGA)[1].

Biological function

Minoxidil is a mitogenic drug used to treat arterial hypertension due to its vasodilator effect. It has also been used as a cosmetic drug since it stimulates hair follicles to promote hair growth. Minoxidil is a potent arteriolar vasodilator that opens potassium channels on the peripheral artery's smooth muscles, causing hyperpolarization of the cell membrane. Xu et al. suggested that K+-channel activity is necessary for progression to the G1 stage of the cell cycle; therefore, it might play a key role in cell proliferation at the early stage. An animal study demonstrated that Minoxidil increased cellular DNA synthesis and enhanced cell proliferation.

Mechanism of action

Although the mechanism of action of Minoxidil is still unclear, it is suggested that its vasodilatory effect increases blood flow at the level of the dermal papilla, which favors local irrigation and follicular proliferation of matrix cells. The positive impact of Minoxidil on hair growth is mainly due to its metabolite, minoxidil sulfate, and the enzyme responsible for this conversion is sulfotransferase, which is located in hair follicles and varies in production among individuals. To exert its hair-growing effect, Minoxidil must be sulfonated in the scalp by the minoxidil sulfotransferase enzyme (SULT1A1). Two phenol sulfotransferases are responsible for minoxidil sulfation in the human scalp, and patients with higher enzyme activity responded better to topical Minoxidil than those with lower enzyme activity[2].

Carcinogenicity

Some researchers suggest that some mitogenic agents, such as Minoxidil, may be potential mutagenic and carcinogenic agents since they act in a dose-dependent manner[3]. Minoxidil is a cosmetic drug recognized as a mitogenic agent, and mitogens are suggested to have carcinogenic and mutagenic potential by inducing cell division and increasing the possibility of perpetuating DNA damage. Mitogenic agents represent a significant factor in carcinogenesis since increasing cell proliferation increases the probability that the genotoxicity present in the cell will perpetuate itself and lead to mutations that can result in the development of cancer. Given that the carcinogenic capacity of mitogenic agents is known. Researchers hypothesized that applying a high dose of topical Minoxidil would increase MNEs in hairless mice. They showed that topical Minoxidil at high doses acted as a genotoxic agent in SKH1 hairless mice, either due to the amount or by its mitogenic effect, as the results showed a statistically significant increase in the numbers of MNEs and MNPCEs. However, whether Minoxidil behaves as a clastogenic or an aneuploidogenic agent is still unknown.

References

[1] Roberts, Janet , et al. "Sulfotransferase activity in plucked hair follicles predicts response to topical minoxidil in the treatment of female androgenetic alopecia." Dermatologic Therapy 27.4(2014):252-254.

[2] Lemes, Luciana Rodino , et al. "Topical and Oral Minoxidil for Hair Disorders in Pediatric Patients: What do we know so far?."Dermatologic Therapy 19(2020).

[3] Eduardo Naranjo-Vázquez, et al. "Effect of High-Dose Topical Minoxidil on Erythrocyte Quality in SKH1 Hairless Mice."Animals 10.4(2020):731.

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