Evaluation of Interactions Between Transient Receptor Potential Vanilloid 1 and Active Constituents Using Molecular Docking

Introduction: Pain, whether acute or chronic, imposes huge economic burdens in the societies due to complexities in the signaling pathways that lead to pain. There are many nociceptive receptors and channels that play key roles in the processing and maintenance of pain. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel that is considered a crucial target in pain. Drugs that are available in the market have side effects, highlighting the need to find new analgesics that have no side effects.
Methods: In this study, we assessed the interactions between active constituents and TRPV1 receptor using molecular docking in comparison to capsazepine and the analgesic drug SB-3567791; 3-(4-chlorophenyl)-N-(3-methoxyphenyl)-2-propenamide. Molecular docking is a computational technique that provides calculation for the non-covalent binding of protein or receptor and ligand molecule(s) and aids in investigating the binding interaction between ligands and receptors. These selected active constituents belong to different classes of secondary metabolites including alkaloids, terpenoids, and flavonoids.
Results: The results indicate promising binding affinities between and TRPV1 receptor and speciofoline, mitragynine, 7-hydroxymitragynine, salvinorin, mescaline, acacetin, ladanein, vulgarin, marrubiin, geranial, neral, epi-α-cadinol (t-cadinol), myrtenol, δ- cadinene, and α-terpineol. The compound α-calacorene showed no affinity toward TRPV1 receptor at all.
Conclusion: Many active compounds are ligands for TRPV1 channel and can be assessed to determine their effects on inhibiting TRPV1 as analgesics. These results allow us to assess the effects of many of these compounds on TRPV1 channel in vivo and in vitro.