Analysis of information sources in references of the Wikipedia article "ATP-sensitive potassium channel" in English language version.
Other potassium channel openers, like diazoxide [39, 40] and pinacidil [41] can cause hypertrichosis in humans as well as minoxidil. In balding macaques minoxidil, cromakalin and P-1075 (a pinacidil analogue) stimulate hair growth in about 20 weeks of topical treatment, whereas a fourth potassium channel opener, called RP49356, is not effective [42].
The evidence that [potassium channel openers (PCOs)] are active on hair growth is correlative. In humans three PCOs have been reported to affect hair growth. Minoxidil was reported to induce hypertrichosis during early clinical trials as an antihypertensive [12]. These side effects were characterized by increasingly visual facial hair, thickening of eyebrows, and diffuse hair growth across the upper back and limbs. Systemic minoxidil induced hypertrichosis in 80–100% of adults [13]. Clinical trials using topical minoxidil demonstrate increased scalp hair in about 39% of treated balding men. Oral diazoxide causes hypertrichosis in most hypoglycemic children and about 1% of adults, and induces some scalp hair in 25% of the balding patients [13–15]. Systemic pinacidil induces hypertrichosis in 2–13% of patients [13]. We are not aware of any topical hair growth trials using pinacidil.
Through its vasodilatory properties [19], minoxidil may enhance blood flow to the scalp, improving oxygen and nutrient delivery to hair follicles, and creating a microenvironment conducive to hair growth [20]. However, studies of organ-cultured hair follicles, which lack a vascular supply, have shown that minoxidil directly stimulates follicular growth via activation of KATP channels in dermal papilla cells [21]. This finding suggests that while vasodilation may contribute to minoxidil's mechanism of action, KATP channel activation is primarily responsible mechanistically. The clinical relevance of this pathway is further supported by Cantu syndrome, in which gain-of-function mutations in KATP channel subunits (SUR2 and KIR6.1) cause hypertrichosis [22].
As mentioned earlier, the hair-growth-promoting properties of minoxidil were clear from initial development. [...] Of concern, if excessive doses are used, even topically, there is the potential for minoxidil to have systemic effects—precipitating a possible "drug-induced Cantú syndrome." Indeed [pulmonary hypertension (PH)], edema, coarsening of facial features, and even reopening of the ductus arteriosus are associated with the Kir6.1/SUR2B active [potassium channel openers (KCOs)] minoxidil and diazoxide (156–158). Multiple KCOs induce and prolong anagen, the rapidly dividing stage of hair, in cultured follicles to promote growth, which can be reversed by the KATP inhibitor tolbutamide (86–88, 159). It is possible that CS-associated mutations have the same hair growth cycle effects, though this requires clarification. Thinking more broadly about the electrical consequences, KATP activation versus voltage-gated calcium channel (VGCC) activation would be expected to have opposing electrophysiological effects, and interestingly Timothy syndrome, caused by gain-of-function mutations in the VGCC, CaV1.2 is associated with baldness at birth (160), potentially the reverse mechanistic phenomenon.
Other potassium channel openers, like diazoxide [39, 40] and pinacidil [41] can cause hypertrichosis in humans as well as minoxidil. In balding macaques minoxidil, cromakalin and P-1075 (a pinacidil analogue) stimulate hair growth in about 20 weeks of topical treatment, whereas a fourth potassium channel opener, called RP49356, is not effective [42].
The evidence that [potassium channel openers (PCOs)] are active on hair growth is correlative. In humans three PCOs have been reported to affect hair growth. Minoxidil was reported to induce hypertrichosis during early clinical trials as an antihypertensive [12]. These side effects were characterized by increasingly visual facial hair, thickening of eyebrows, and diffuse hair growth across the upper back and limbs. Systemic minoxidil induced hypertrichosis in 80–100% of adults [13]. Clinical trials using topical minoxidil demonstrate increased scalp hair in about 39% of treated balding men. Oral diazoxide causes hypertrichosis in most hypoglycemic children and about 1% of adults, and induces some scalp hair in 25% of the balding patients [13–15]. Systemic pinacidil induces hypertrichosis in 2–13% of patients [13]. We are not aware of any topical hair growth trials using pinacidil.
Through its vasodilatory properties [19], minoxidil may enhance blood flow to the scalp, improving oxygen and nutrient delivery to hair follicles, and creating a microenvironment conducive to hair growth [20]. However, studies of organ-cultured hair follicles, which lack a vascular supply, have shown that minoxidil directly stimulates follicular growth via activation of KATP channels in dermal papilla cells [21]. This finding suggests that while vasodilation may contribute to minoxidil's mechanism of action, KATP channel activation is primarily responsible mechanistically. The clinical relevance of this pathway is further supported by Cantu syndrome, in which gain-of-function mutations in KATP channel subunits (SUR2 and KIR6.1) cause hypertrichosis [22].
As mentioned earlier, the hair-growth-promoting properties of minoxidil were clear from initial development. [...] Of concern, if excessive doses are used, even topically, there is the potential for minoxidil to have systemic effects—precipitating a possible "drug-induced Cantú syndrome." Indeed [pulmonary hypertension (PH)], edema, coarsening of facial features, and even reopening of the ductus arteriosus are associated with the Kir6.1/SUR2B active [potassium channel openers (KCOs)] minoxidil and diazoxide (156–158). Multiple KCOs induce and prolong anagen, the rapidly dividing stage of hair, in cultured follicles to promote growth, which can be reversed by the KATP inhibitor tolbutamide (86–88, 159). It is possible that CS-associated mutations have the same hair growth cycle effects, though this requires clarification. Thinking more broadly about the electrical consequences, KATP activation versus voltage-gated calcium channel (VGCC) activation would be expected to have opposing electrophysiological effects, and interestingly Timothy syndrome, caused by gain-of-function mutations in the VGCC, CaV1.2 is associated with baldness at birth (160), potentially the reverse mechanistic phenomenon.
As mentioned earlier, the hair-growth-promoting properties of minoxidil were clear from initial development. [...] Of concern, if excessive doses are used, even topically, there is the potential for minoxidil to have systemic effects—precipitating a possible "drug-induced Cantú syndrome." Indeed [pulmonary hypertension (PH)], edema, coarsening of facial features, and even reopening of the ductus arteriosus are associated with the Kir6.1/SUR2B active [potassium channel openers (KCOs)] minoxidil and diazoxide (156–158). Multiple KCOs induce and prolong anagen, the rapidly dividing stage of hair, in cultured follicles to promote growth, which can be reversed by the KATP inhibitor tolbutamide (86–88, 159). It is possible that CS-associated mutations have the same hair growth cycle effects, though this requires clarification. Thinking more broadly about the electrical consequences, KATP activation versus voltage-gated calcium channel (VGCC) activation would be expected to have opposing electrophysiological effects, and interestingly Timothy syndrome, caused by gain-of-function mutations in the VGCC, CaV1.2 is associated with baldness at birth (160), potentially the reverse mechanistic phenomenon.
