Affinity of Granisetron for glutamate N-methyl-D-aspertate receptor to evaluate antidepressant activity by Docking studies

Background: Depressive disorders are major public health concern worldwide. The currently used drugs are associated with low success rate and significant drug related adverse effects. Therefore there is a focus for the development of drugs acting on different targets. As N-methyl-D-aspertate [NMDA] receptors are involved in the pathophysiology of depression, the present study was undertaken to evaluate the affinity of granisetron on glutamate NMDA receptors. Materials and Methods: Protein sequence of NMDA receptor of Homo sapiens was retrieved from the NCBI database. The three dimensional structure of NMDA receptor was modeled using SWISS MODEL modeling server and RAMPAGE was used to validate the modeled structure. Molecular structures of test drug, granisetron and control drug, ketamine were retrieved from the PubChem. Docking studies was performed using Hex software. Results: Homology modeled protein structure validation showed about 90.2% of residues in favorable region. Docking results revealed that granisetron showed the energy value of -246.18 which is much acceptable compared to energy values of already proven molecule, ketamine i,e -176.31. Conclusion: Targeting the NMDA receptor is the new strategy for the depression disorder and ketamine is the proved drug which is used to target the NMDA receptor for the depression. By comparing the energy values this study showed that, granisetron also to be a potent molecule compared with the ketamine. Based on this data further animal studies need to be performed to understand the safety profile of the drug.