Allosteric Targeting of the Dopamine D2 Receptor

One-third of medicines target proteins called G protein-coupled receptors (GPCRs), which are found all over the body and are involved in numerous diseases and disorders. One example is the common mental disorder schizophrenia, in which there is an excessive activity of a chemical messenger within the brain. The chemical messenger causes its effect by interacting with a GPCR known as the dopamine receptor. Current medicines completely block this interaction but cause severe side-effects. We have identified a drug that only partially blocks the action of the chemical messenger. This thesis investigates the mechanism of action behind this novel action. Understanding this mechanism will potentially allow for the rational design of improved drugs for this important therapeutic target.