Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides

Abstract

Dopaminergic receptor system has been in focus for the development of new pharmacotherapeutic agents, targeting number of central nervous system related disorders, like drug addiction, schizophrenia, depression, and Parkinson's disease, just to name a few. So far crystal structure for human D2 receptor is not known, despite it’s vital function and importance as therapeutic target. Here we present, recent progress in determination of the key receptor-ligand interactions for available arylpiperazine like ligands, using D2 receptor model, based upon crystal D3 receptor structure. To determine key interactions responsible for high dopaminergic activity, we used computer docking analysis together with experimental data. Total of 4 dopaminergic ligands showing moderate to high affinity, were tested and obtained results rationalized using ligand structures docked into proposed D2 receptor model. [Projekat Ministarstva nauke Republike Srbije, br. 172032]

Keywords

• arylpiperazine
• GPCR
• docking
• molecular modeling