(-)-Incarvillateine (INCA) is a monoterpene alkaloid produced by Incarvillea sinensis that has been used as a pain reliever in China for a long time. Previous work by our group has identified truxillic acid monoesters (TAMEs) as a new class of inhibitors targeting fatty acid binding protein 5 (FABP5) and showing both antinociceptive and anti-inflammatory effects in mouse models. Due to the structural similarity between INCA and TAMEs, we hypothesized that INCA could exert its antinociceptive effects via FABP inhibition. Our findings show that INCA does not bind to four human FABP isoforms (FABP3, FABP4, FABP5 and FABP7) in vitro and the putative monoester metabolite of INCA, INCA-TAME, which closely resembles TAMEs also lacked affinity for FABPs. Further investigation in mouse studies showed that INCA exerts not only potent antinociceptive but also motor suppressive effects at equivalent doses while INCA-TAME was ineffective. This result implies that the observed antinociceptive effects of INCA should be interpreted with caution.

Incarvillateine produces antinociceptive and motor suppressive effects via adenosine receptor activation

2019 Spring National Meeting

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