HARMINE INTERACTION WITH MU OPIOID RECEPTOR IN COMPARISON WITH CODEINE BY DOCKING METHOD: IN SILICO STUDY

Background and Aim : Opioids are well-known useful analgesics. However, abuse and addiction are the challenges, which are associated with the opioid analgesic usage. The three known opioid receptors, mu, delta and kappa, play a key role in pain control also hedonic homeostasis, mood and well-being. Codeine, a naturally occurring alkaloid derived from Papaver somniferum, is commonly used to relieve chronic pain. Peganum harmala is a known plant in herbal medicine and its active alkaloids can produce different pharmacological and therapeutic effects. In this regard, harmine is a beta-carboline alkaloids from Peganum harmala, and it is known that P. harmala-derived beta-carbolines interact with opioid receptors and several other receptors in the nervous system, so they would induce many pharmacological effects. According to the adverse effects of codeine, including tolerance and dependence, we intended to evaluate the interaction of harmine with mu opioid receptor in comparison with codeine by in silico docking method. This might be an initial step in estimating the possibility of substitution of harmine for codeine. Methods : Protein structure of mu opioid receptor was taken from Protein Data Bank with PDB ID: 5C1M. The molecular structures of harmine (CID_5280953) and codeine (CID_5284371) were obtained from PubChem. We used Chimera 1.8 for protein editing and building the pdb files; moreover, MGLTools 1.5.6, AutoDockTools-1.5.6 and AutoDock4 were used to complete docking process. Because this crystal structure of mu receptor included chain A and B, chain A of mu receptor was selected for docking procedure.Results : The inhibition constant (Ki) of harmine and codeine in interaction with mu opioid receptor were 544.9 nM and 17.67 nM, respectively. Conclusion : The docking results revealed that codeine had lower Ki than harmine. Therefore, harmine seems to show lower affinity to chain A of mu opioid receptor due to higher harmine Ki resulted from docking evaluation. Then, the lower affinity of harmine to chain A of mu opioid receptor may lead to suppose reduced adverse effects in comparison with codeine. The experimental studies is extremely recommended for more explaining about the effects of harmine on opioid receptors

Keywords:

Harmine , Codeine , Opioid receptor , Docking