Dopamine receptors perform various functions essential to vertebrate central nervous systems and they are the major targets of antipsychotic drugs. Our recent studies pioneered to perform molecular modeling studies of the dopamine D2 receptor (D2R), describing the mechanism and binding affinities of marketed antipsychotics into the active sites of the D2highR and D2LowR [1]. Another study provided significant information about changes of binding cavity properties of D2R [2].

Since the marketed antipsychotics have serious side effects, we aim to explore ligands with better inhibition profiles on D2R with less unwanted outcomes. For this aim, we compare the effectiveness of the marketed drugs with small peptides and vitamin substances.

The main goal of the research is to explore novel small molecules that inhibit D2R to be used in schizophrenia.

In this study, we used a large number of endogen vitamins and peptides with dopamine D2R active-inactive forms in monomeric-dimeric patterns to understand their interactions at the active sites of targets. Nineteen of antipsychotic drugs, which are widely used in schizophrenia treatment are selected as reference molecules. Molecular docking, molecular screening and molecular modeling approaches were used.

Some of these endogen molecules showed similar or better inhibition profiles on D2R compared to the known standard inhibitors of the target.

Proposed molecules may be potent for D2 receptor inhibition with less side effects for the use for schizophrenia.

The authors have not supplied their declaration of competing interest.