Antinociceptive effect of natural and synthetic alkamides involves TRPV1 receptors.

OBJECTIVE To establish the role of TRPV1 receptor in the antinociceptive effect of natural alkamides (i.e. affinin, longipinamide A, longipenamide A and longipenamide B) isolated from Heliopsis longipes (A. Gray) S.F. Blake and some related synthetic alkamides (i.e. N-isobutyl-feruloylamide and N-isobutyl-dihydroferuloylamide). METHODS The orofacial formalin test was used to assess the antinociceptive activity of natural (1-30 μg, orofacial region) and synthetic alkamides (0.1-100 μg, orofacial region). The alkamide capsaicin was used as positive control, while capsazepine was used to evaluate the possible participation of TRPV1 receptor in alkamide-induced antinociception. KEY FINDINGS Natural (1-30 μg) and synthetic (0.1-100 μg) alkamides administered to the orofacial region produced antinociception in mice. The antinociceptive effect induced by affinin, N-isobutyl-feruloylamide and N-isobutyl-dihydroferuloylamide was antagonized by capsazepine but not by vehicle. CONCLUSIONS These results suggest that alkamide affinin, longipinamide A, longipenamide A and longipenamide B isolated from Heliopsis longipes as well as the synthesized analogue compounds N-isobutyl-feruloylamide and N-isobutyl-dihydroferuloylamide produce their effects by activating TRPV1 receptor and they may have potential for the development of new analgesic drugs for the treatment of orofacial pain.