Comparison of Efficacy of Nicotine Vs Plant based Alkaloid in Addiction - An In-Silico Study

Abstract

Introduction: Nicotine addiction remains a global health challenge, contributing significantly to preventable morbidity and mortality. While nicotine replacement therapies (NRTs) offer some relief, their limited success rates and potential carcinogenic risks underscore the need for safer, plant-derived alternatives. Phytotherapeutic agents like lobeline, a natural alkaloid from Lobelia species, have demonstrated neuropharmacological activity via interaction with nicotinic acetylcholine receptors (nAChRs).

Objectives: This study aims to evaluate and compare the binding affinity of lobeline, a plant-based alkaloid, with that of nicotine to nAChRs using in-silico docking models, and to highlight the therapeutic advantages of phytotherapeutic agents in addiction management.

Methods: Molecular docking simulations were performed using AutoDock 4.2 to predict binding interactions between ligands (lobeline and nicotine) and the α4β2 subunit of the nicotinic acetylcholine receptor. Ligand structures were retrieved from ZINC and ChEMBL databases, and receptor files were preprocessed for docking. Docked complexes were analyzed for binding affinity (ΔG), hydrogen bonds, and amino acid interactions using PyMOL and Discovery Studio.

Results:  Lobeline demonstrated a higher binding affinity (-8.14 kcal/mol) compared to nicotine (-3.8 kcal/mol). Key amino acid residues involved in lobeline’s interaction included Val, His, Ala, and Tyr, whereas nicotine interacted mainly with His. These findings suggest stronger and more specific binding for lobeline at the receptor site. 

Conclusions: Lobeline, owing to its superior receptor-binding affinity and neuropharmacological advantages, presents a promising phytotherapeutic alternative to nicotine in addiction therapy. The results emphasize the potential role of plant-based compounds in developing safer and more effective interventions for nicotine dependence.