Measuring Affinity of Ligands to the Oxytocin Receptor Using Radioligand Binding

Two aims of oxytocin receptor (OTR)-targeted drug discovery are development of selective OTR-binding PET tracers and development of brain-permeable selective OTR agonists. By allowing measurement of central OTR binding site occupancy after administration of intranasal oxytocin, OTR PET tracers inform an understanding of the conflicting effects on pro-social behaviors seen with administration of intranasal oxytocin in human studies. By mitigating pharmacokinetic and pharmacodynamic limitations of intranasal oxytocin, development of brain-permeable selective OTR agonists may produce therapies for mental disorders that involve asocial symptoms. A key step in development of new OTR-targeting PET radioligands and small molecule agonists is measurement of OTR affinity. One technique that can quantitate the affinity of candidate ligands for the OTR is competition radioligand binding. This chapter describes the materials, methods, and considerations of experimental design required to conduct the steps of competition radioligand binding for OTR drug discovery.