Title : Phytomolecules as nicotinic receptor modulators: A novel strategy for combating nicotine addiction
Abstract:
Nicotine addiction is a major global health challenge, necessitating the development of innovative therapeutic solutions beyond conventional pharmacological interventions, such as nicotine replacement therapy and synthetic receptor modulators, which often exhibit limited efficacy and adverse side effects. Recent research highlights the potential of phytomolecules i.e.bioactive compounds derived from plants—as promising alternatives for modulating nicotinic acetylcholine receptors (nAChRs). These natural compounds exert their effects through diverse mechanisms, including competitive and non-competitive inhibition, allosteric modulation, and receptor desensitization, thereby influencing nicotine's neuropharmacological impact.Among nAChRs, the α4β2 and α7 subtypes play critical roles in nicotine dependence, with partial agonists demonstrating therapeutic potential by modulating receptor activity, alleviating withdrawal symptoms, and reducing relapse risk. Several bioactive phytomolecules, including cytisine, lobeline, anatabine, nornicotine, coniine, and arecoline, exhibit partial agonist activity at these receptors offering natural alternatives or adjuncts to synthetic drugs like varenicline.Besides, bioactive compounds of C. sinensis and M.oleifera shows potential as α-2 nAChR inhibitors.Additionally, some plant-derived compounds such as Theaflavin-3-Gallate, Asiaticoside, and Theaflavin-3,3-Digallate are also identified as potent inhibitors of specific nAChR subtypes, including α3 and α2, expanding the therapeutic landscape for nicotine dependence.In this way, by leveraging the receptor-modulatory effects of phytomolecules, novel, plant-based therapeutic strategies can be developed, offering safer, more accessible, and effective options for nicotine addiction treatment.
Keywords: Nicotine addiction, nAChRs , Bioactive Phytomolecule, Receptor modulation, Natural inhibitors, Therapeutic strategies
