Theoretical insights into the mechanism of action of atypical antipsychotics

The present work discusses some theoretical mathematical results that can be derived from the theory of receptor binding linked with PET experimental data and presents insights to the understanding of the differences between typical and atypical profile of antipsychotics regarding the generation of extrapyramidal syndrome. The first part of the paper discusses the importance of the drug affinity to dopamine D2 receptors (D2R) and of the therapeutic window of drug concentration for antipsychotic action without EPS, whereas the second part discusses the contribution of the plasma half-life in the time-course of D2R occupancy. Together with current experimental data, we concluded that the key factors leading to an atypical profile would be adequate posology, low affinity of the drug to D2R and/or short plasma half-life.