title: Identification of multi-targeted anti-migraine potential of nystatin and development of its brain targeted chitosan nanoformulation.
abstract: The complex pathophysiology involved in migraine necessitates the drug treatment to act on several receptors simultaneously. The present investigation was an attempt to discover the unidentified anti-migraine activity of the already marketed drugs. Shared featured pharmacophore modeling was employed for this purpose on six target receptors (β2adrenoceptor, Dopamine D3, 5HT1B, TRPV1, iGluR5 kainate and CGRP), resulting in the generation of five shared featured pharmacophores, which were further subjected to virtual screening of the ligands obtained from Drugbank database. Molecular docking, performed on the obtained hit compounds from virtual screening, indicated nystatin to be the only active lead against the receptors iGluR5 kainate receptor (1VSO), CGRP (3N7R), β2adrenoceptor (3NYA) and Dopamine D3(3PBL) with a high binding energy of -11.1, -10.9, -10.2 and -12kcal/mole respectively. The anti-migraine activity of nystatin was then adjudged by fabricating its brain targeted chitosan nanoparticles. Its brain targeting efficacy, analyzed qualitatively by confocal laser scanning microscopy, demonstrated a significant amount of drug reaching the brain. The pharmacodynamic models on Swiss male albino mice revealed significant anti-migraine activity of the nanoformulation. The present study reports for the first time the therapeutic potential of nystatin in migraine management, hence opening avenues for its future exploration.
authors.affiliation: Department of Pharmaceutical Sciences, G. J. University of Sci. & Tech., Hisar 125001, India. Electronic address: ph.arora13@gmail.com.
authors.forename: Priti
authors.initials: P
authors.lastname: Girotra
authors.affiliation: Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, India.
authors.forename: Aman
authors.initials: A
authors.lastname: Thakur
authors.affiliation: Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Sciences, G. J. University of Sci. & Tech., Hisar 125001, India.
authors.forename: Shailendra Kumar
authors.initials: SK
authors.lastname: Singh
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D065546:Drug Liberation; D006120:Grooming / Q000187:drug effects; D006930:Hyperalgesia / Q000150:complications; D008297:Male; D051379:Mice; D008881:Migraine Disorders / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry*; D009761:Nystatin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010316:Particle Size; D020795:Photophobia / Q000139:chemically induced / Q000150:complications; D011487:Protein Conformation; D012984:Software
chemical_list: D004337:Drug Carriers; D009761:Nystatin; D048271:Chitosan; D001920:Bradykinin
keywords: Chitosan; Migraine; Molecular docking; Nystatin; Pharmacophore modeling