Abstract

On the basis of the ability of capsaicin to activate the transient receptor potential vanilloid 1 receptor (TRPV1) expressed in nociceptive sensory neurons, topical and injectable high-concentration formulations are being developed as potential treatments for various pain syndromes. As much of the published literature on capsaicin is based on pepper extracts, which are typically a mixture of capsaicin and other capsaicinoids (including norhydrocapsaicin, dihydrocapsaicin, homocapsaicin and homodihydrocapsaicin), the purpose of this investigation was to study the in vitro metabolism of pure capsaicin. The metabolism of capsaicin was similar in human, rat, and dog microsomes and S9 fractions. In these assays, three major metabolites were detected and identified as 16-hydroxycapsaicin, 17-hydroxycapsaicin, and 16,17-dehydrocapsaicin. In addition to these three metabolites, rat microsomes and S9 fractions also produced vanillylamine and vanillin. Biotransformation of capsaicin was slow in human skin in vitro, with the majority of the applied capsaicin remaining unchanged and a small fraction being metabolized to vanillylamine and vanillic acid. These data suggest that the metabolism of capsaicin by cytochrome P450 enzymes in skin is minimal, relative to hepatic metabolism.