Comparative receptor pharmacology of antipsychotic drugs based on normalized binding affinity data and breadth of interaction.

The pharmacology of antipsychotic drugs (APDs) is exceedingly complex with many of them showing a broad receptor interaction spectrum. We aimed to provide a reference work on receptor binding affinity, to quantify the breadth of receptor interaction of APDs and to analyze implications on clinical efficacy and classification. Binding affinity data were obtained from an open-source database and normalized to allow for direct comparison of affinity profiles across compounds and quantification of the receptor interaction breadth at the level of (1) individual drugs and (2) defined receptor groups. Breadth data were correlated with clinical efficacy data taken from the literature and analyzed in relation to chemical structure and taxonomy, particularly the Neuroscience-based Nomenclature (NbN). Normalized affinity profiles of 35 worldwide used APDs for 25 receptors and receptor interaction breadth for drugs and defined receptor groups were calculated and presented in graphical and tabular form. High breadth values were associated with tricyclic basic structure but were not associated with clinical efficacy. The NbN classification did not show full correspondence with our in-depth statistical analysis of receptor group-related breadth values. In sum, our study provides a representative multireceptor profiling of the worldwide most frequently used APDs and offers a way to quantify and compare the breadth of receptor interaction at the level of individual compounds as well as receptor groups within compounds.