The opening of intracellular potassium channels has been suggested as a mechanism
regulating hair growth. Enhancing the flux of potassium ions is a mechanism shared by
several structurally diverse antihypertensive agents including minoxidil sulfate (the
active metabolite of minoxidil), pinacidil, P-1075 (a potent pinacidil analog), RP-49,356,
diazoxide, cromakalim, and nicorandil. Of these drugs, minoxidil, pinacidil, and diazoxide
have been reported to elicit hypertrichosis in humans. This potassium channel hypothesis
was examined by testing these drugs for effects on hair growth both in vitro and in vivo.
For the in vitro studies, mouse vibrissae follicles were cultured for 3 d with drug and
the effects on hair growth were measured by metabolic labeling. All drugs, except
diazoxide, enhanced cysteine incorporation into the hair shafts of the cultured vibrissae.
Diazoxide was poorly soluble and thus was tested only at low doses. Minoxidil, P-1075,
cromakalim, and RP-49,356 were also evaluated in vivo by measuring hair growth effects in
balding stumptail macaque monkeys. The drugs were administered topically to defined sites
on balding scalps once per day for 4-5 months and the amount of hair grown was determined
by monthly measurements of shaved hair weight. Three of the drugs produced significant
increases in hair weight whereas, the RP-49,356 had no effect. These studies provide
correlative evidence that the opening of potassium channels is an important regulatory
mechanism for hair growth. This provides the impetus for further studies on this
potentially important mechanism affecting hair biology.