Analysis of Drug Interactions with Dopamine Receptor by Frontal Analysis and Cell Membrane Chromatography

Abstract

Determining the interactions between drugs and receptors is very important in revealing the activity and mechanism of drugs. The dopamine receptor was purified from rat brain tissue and immobilized on the surface of silica gel to prepare the stationary phase. From the model of frontal analysis conducted with DAR/CMC columns, the dissociation equilibrium constants (K D) were (4.87 ± 0.35) × 10−6 M for dopamine, (5.58 ± 0.20) × 10−7 M for olanzapine, (5.22 ± 0.12) × 10−7 M for quetiapine, (4.50 ± 0.37) × 10−7 M for bupropion, and (3.41 ± 0.28) × 10−7 M for domperidone. The affinity order conducted by frontal analysis had a positive correlation with the k values of the antagonists. Competitive binding study showed that domperidone, bupropion, quetiapine and olanzapine occupied certain binding sites of DAR on the column, thus hindering the association of dopamine. In addition, hydrophobic interaction was the main force for domperidone, bupropion and dopamine to bind with DAR. For quetiapine and olanzapine, hydrogen bond or Van der Waals force is the major factor contributing to the interaction. The studies showed that CMC could be applied to the investigation of drug–receptor interactions.