Abstract
Minoxidil, in addition to its effect on hypertension and hair growth, has been proposed as a potential antifibrotic agent. Minoxidil inhibits the contraction of collagen lattices by human fibroblasts in vitro. However, the mechanism of inhibition is unknown. As minoxidil is metabolised in the body to minoxidil glucuronide and minoxidil sulphate, we investigated the potencies of these metabolites to inhibit collagen lattice contraction. We also studied selected analogues of minoxidil to assess the influence of certain functional groups in the inhibition. The major metabolite, minoxidil glucuronide, proved to be inactive, whereas minoxidil sulphate was considerably more active than minoxidil. In terms of the structural analogues, the substitution of one amino group by a methyl group resulted in loss of the inhibitory activity; removal of the nitroxide oxygen led to stronger inhibition than with minoxidil. Further studies are planned to learn more about a possible role for minoxidil in wound contraction.
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