Investigation of chemical interactions of small peptides and vitamin substances at the developed dopamine D2 receptor models

Abstract

Introduction

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 D2^highR and D2^LowR [1]. Another study provided significant information about changes of binding cavity properties of D2R [2].

Objectives

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.

Aims

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

Methods

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.

Results

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

Conclusions

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

Disclosure of interest

The authors have not supplied their declaration of competing interest.