EVALUATION OF VALERENIC ACID INTERACTION WITH DELTA OPIOID RECEPTOR IN COMPARISON WITH METHADONE BY IN SILICO DOCKING METHOD

Background and Aim : Opioids has been used as analgesics from previous millennia till now. In contrast, abuse and addiction are the problems that accompanied with the opioid analgesic usage. There are three opioid receptors, Mu, delta and kappa that play a main role in pain control also mood and well-being. Delta opioid receptor is involved in addiction process. In this regard, methadone is one of the drugs that is recommended as a first line treatment for medically assisted withdrawal from opioids as heroin. Although methadone as a high efficacy mu-agonist is relatively selective for mu-receptor versus other types of opioid receptor, there is an evidence that suggests about the change of methadone antinociception to a delta receptor response. Valerian root extracts from the genus Valeriana (Valerianaceae) have been used for centuries in popular medicine for the treatment of anxiety, epilepsy, and sleep disorders. Accordingly, we intended to evaluate valerenic acid, a main component of valerian root extracts, interaction with delta opioid receptor in comparison with methadone by in silico docking method. This might be a first step in evaluating the possibility of substitution of valerenic acid for methadone. Methods : Protein structure of delta opioid receptor was chosen from Protein Data Bank with PDB ID: 4EJ4. The molecular structures of methadone (CID_4095) and valerenic acid (CID_6440940) were obtained from PubChem. Chimera 1.8 was used for protein editing and making the pdb files. Also, MGLTools 1.5.6, AutoDockTools-1.5.6 and AutoDock4 were applied to accomplish docking process. Results : The inhibition constant (Ki) of methadone and valerenic acid in interaction with delta opioid receptor were 5.36 nM and 947.18 nM, respectively. Conclusion : The docking results revealed that methadone presented lower Ki than valerenic acid. Thus, valerenic acid seems to show lower affinity to delta opioid receptor due to valerenic acid higher Ki. Then, the lower affinity of valerenic acid to delta receptor may lead to reduced adverse effects in comparison with methadone. The evaluation of valerenic acid interaction with mu receptor and experimental studies is highly recommended to clarify the effects of valerenic acid

Keywords:

Valerenic acid , Methadone , Opioid receptor , Docking