Brain Receptor Occupancy: A Measure for Pharmacological Activity?

It has become possible to investigate the pharmacodynamic effect of antipsychotic and antidepressive drugs in vivo with the development of neuroimaging techniques. Especially functional neuroimaging offers the ability to analyze metabolic alterations and neuroreceptor-systems of the human brain in order to gain a more detailed knowledge of the molecular-biological level underlying clinical symptoms.

Our team focuses on quantative analysis of receptor occupancy by means of positron emission tomography (PET) and single photon emission computerized tomography (SPECT). Our current studies emphasize the role of brain receptor occupancy in psychopharmacological research.

Up-to-date dosing regimens of psychotropic drugs are based on plasma kinetic considerations, although it is a matter of debate whether plasma levels faithfully reflect brain kinetics of drugs. Current studies of brain kinetics applying functional neuroimaging techniques may provide a sounder basics for determining dosing schedules of psychotropic medicine. Data of our recent study on Risperdal consta support that theory.

As it has been demonstrated by several groups the rate of EPS (extrapyramidal syndrome) side effects of atypical antipsychotics dramatically increases with a striatal D₂-occupancy of more than 80%. SPECT/PET imaging has been used as an attempt to understand differences between antipsychotic drugs in terms of efficacy and side effect profiles. We explored the relationship between striatal D₂-occupancy and EPS in bipolar patients receiving the atypical antipsychotic olanzapine.

Functional neuroimaging has probably not been established as a part of a routine clinical diagnosis yet but it has become indispensable in visualizing the place of drug-action.