A quantum chemical approach representing a new perspective concerning agonist and antagonist drugs in the context of schizophrenia and Parkinson’s disease

Schizophrenia and Parkinson’s disease can be controlled with dopamine antagonists and agonists. In order to improve the understanding of the reaction mechanism of these drugs, in this investigation we present a quantum chemical study of 20 antagonists and 10 agonists. Electron donor acceptor capacity and global hardness are analyzed using Density Functional Theory calculations. Following this theoretical approach, we provide new insights into the intrinsic response of these chemical species. In summary, antagonists generally prove to be better electron acceptors and worse electron donors than dopamine, whereas agonists present an electron donor-acceptor capacity similar to that of dopamine. The chemical hardness is a descriptor that captures the resistance of a chemical compound to change its number of electrons. Within this model, harder molecules are less polarizable and more stable systems. Our results show that the global hardness is similar for dopamine and agonists whilst antagonists present smaller values. Following the Hard and Soft Acid and Bases principle, it is possible to conclude that dopamine and agonists are hard bases while antagonists are soft acids, and this can be related to their activity. From the electronic point of view, we have evolved a new perspective for the classification of agonist and antagonist, which may help to analyze future results of chemical interactions triggered by these drugs.