Antinociceptive properties produced by the pregnane compound velutinol A isolated from Mandevilla velutina

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 E2 (PGE2, 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 μM) did not significantly interfere with the specific binding sites of [3H]resiniferatoxin or [3H]BK in vitro. Our data also suggest that these effects are related with its ability to interact with kinin B1 receptor-mediated mechanisms, as the cotreatment of mice with velutinol A (10 nmol/paw) consistently blocked the nociceptive response induced by the selective B1 receptor agonist des-Arg9-BK. Finally, the persistent hyperalgesia produced by intraplantar injection of carrageenan (300 μg/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 B1-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 B1 receptor pathways.