Velutinol A is a pregnane compound isolated from the rhizomes of the Brazilian plant Mandevilla velutina that interferes with
kinin actions and possesses anti-inflammatory action. Here, we investigate the effect produced by
velutinol A in different models of inflammatory nociception. The nociceptive effect caused by the intraplantar injection of
phorbol myristate acetate (PMA, 50 pmol/paw) in mice was practically abolished by coadministration of
velutinol A (1-10 nmol/paw). In contrast, the coadministration of
velutinol A (10 nmol/paw) failed to affect the nociceptive response elicited by either
bradykinin (BK, 10 nmol/paw) or
prostaglandin E(2) (
PGE(2), 10 nmol/paw). Of note,
velutinol A (10 nmol/paw) partially inhibited the nociceptive response caused by
capsaicin (1 nmol/paw). However,
velutinol A (10 microM) did not significantly interfere with the specific binding sites of [(3)H]
resiniferatoxin or [(3)H]BK in vitro. Our data also suggest that these effects are related with its ability to interact with
kinin B(1) receptor-mediated mechanisms, as the cotreatment of mice with
velutinol A (10 nmol/paw) consistently blocked the nociceptive response induced by the selective B(1) receptor agonist des-Arg(9)-BK. Finally, the persistent
hyperalgesia produced by intraplantar injection of
carrageenan (300 microg/paw) was completely reversed by the coadministration of
velutinol A (10 nmol/paw). Collectively, the present results show that the pregnane compound
velutinol A produces peripheral antinociceptive action in some models of acute and persistent inflammatory
pain by interacting with
kinin B(1)-receptor mediated effects. Thus,
velutinol A or its derivatives could constitute an attractive molecule of interest for the development of new
analgesic drugs. Additional studies are now in progress in order to further explore its precise mechanism of action on B(1) receptor pathways.