Gingerols: a novel class of vanilloid receptor (VR1) agonists

1 Gingerols, the pungent constituents of ginger, were synthesized and assessed as agonists of the capsaicin-activated VR1 (vanilloid) receptor. 2 [6]-Gingerol and [8]-gingerol evoked capsaicin-like intracellular Ca2+ transients and ion currents in cultured DRG neurones. These effects of gingerols were blocked by capsazepine, the VR1 receptor antagonist. 3 The potency of gingerols increased with increasing size of the side chain and with the overall hydrophobicity in the series. 4 We conclude that gingerols represent a novel class of naturally occurring VR1 receptor agonists that may contribute to the medicinal properties of ginger, which have been known for centuries. The gingerol structure may be used as a template for the development of drugs acting as moderately potent activators of the VR1 receptor.