IN SILICO ANALYSIS OF ANTIHISTAMINE DRUGS AS NEUROPROTECTANTS TARGETING DOPAMINE D2-LIKE RECEPTORS IN PARKINSON’S DISEASE

Abstract

Among several neurodegenerative disorders, Parkinson’s is one of the utmost widespread diseases, occur due to the degeneration of the dopaminergic neurons in the region of midbrain which is identified by motor signs like tremor & bradykinesia; non-motor features (like impaired vision, depression, sleeping disorders). Currently, there is no treatment available that can cure PD. However, there is an imbalance between signaling pathway in the basal ganglia circuit. The direct pathway is downregulated and mediated via dopamine D1-like receptors. In contrast, the indirect pathway is upregulated and this is mediated via dopamine D2-like receptors. Using dopamine D2-like receptors antagonists, PD symptoms can be ameliorated. Increased histaminergic signaling has been observed in PD. Herein, we want to analyze the interaction between approved antihistamine drugs with dopamine D2-like receptors. We curated a list of 58 approved antihistamine drugs to analyze their affinity with dopamine D2-like receptors as an inhibitor. Literature indicates a substantial correlation between the antihistamines and dopamine D2-like receptors. Thus, targeting these drugs might regulate the disrupted indirect pathway in the basal ganglia circuit. Through molecular docking analysis, we identified that bilastine, a highly potent and selective inhibitor of histamine H1 receptor shows high affinity with dopamine D2-like receptors and might inhibit the aberrant signaling cascade of indirect pathway and upregulated histaminergic signaling simultaneously. Further studies are required to determine the action.