{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:20:56Z","timestamp":1787840456794,"version":"build-2784847793"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"\n Aim:<\/jats:title>\n \n This study aims to design and develop novel lidocaine analogs specific for the Na\n v<\/jats:sub>\n 1.7 channel using\n in silico<\/jats:italic>\n approaches.\n <\/jats:p>\n <\/jats:sec>\n \n Background:<\/jats:title>\n \n Neuropathic pain (NP) is defined as chronic pain originating from abnormalities found within the nervous system. Voltage-gated sodium channels play a significant role in enhancing neuronal excitability, thus gained significance as a crucial target for developing drugs to treat NP. It consists of 9 different isoforms, with Na\n v<\/jats:sub>\n 1.7 predominantly found in the dorsal root ganglion, playing a crucial role in the pathophysiology of NP. The selective inhibitors targeting the Na\n v<\/jats:sub>\n 1.7 channel hold greater potential for treating NP while minimizing interference with the physiological functions of other sodium channel isoforms.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Atom and field-based three-dimensional (3D) quantitative structure\u2013activity relationship (QSAR) was created using lidocaine analogs to identify the structural features required for the Na\n v<\/jats:sub>\n 1.7 inhibitory activities. Further, the molecular interaction of the scaffold with the Na\n v<\/jats:sub>\n 1.7 channel VSD4 was studied by docking the molecules with it followed by absorption, distribution, metabolism, and excretion (ADME) analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The 3D QSAR studies revealed that the presence of hydrophobic groups and steric parameters heightened the specificity for Na\n v<\/jats:sub>\n 1.7 channel. Docking analysis revealed that 4 compounds, i.e., A15, A14, A6, and A5, exhibited the highest binding affinity in comparison to reference drug lidocaine. Furthermore, ADME predictions indicated that the compounds exhibited favorable characteristics in terms of oral bioavailability and solubility.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n This research offers valuable structural insights to improve the specific inhibition of the Na\n v<\/jats:sub>\n 1.7 channel, facilitating the design and development of novel, Na\n v<\/jats:sub>\n 1.7 channel-specific inhibitors.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/ijabmr.ijabmr_347_24","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T20:01:22Z","timestamp":1755720082000},"page":"143-151","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Three-dimensional Quantitative Structure\u2013activity Relationship, Molecular Docking and Absorption, Distribution, Metabolism, and Excretion Studies of Lidocaine Analogs Pertaining to Voltage-gated Sodium Channel Nav1.7 Inhibition for the Management of Neuropathic Pain"],"prefix":"10.4103","volume":"15","author":[{"given":"Shiwani","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Biophysics, Panjab University, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Rana","sequence":"additional","affiliation":[{"name":"University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelima","family":"Dhingra","sequence":"additional","affiliation":[{"name":"University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanzeer","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Panjab University, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"R1-20250821","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.pain.2013.11.013","article-title":"Neuropathic pain in the general population: A systematic review of epidemiological studies","volume":"155","author":"van Hecke","year":"2014","journal-title":"Pain"},{"key":"R2-20250821","doi-asserted-by":"crossref","first-page":"2058738419838383","DOI":"10.1177\/2058738419838383","article-title":"The neuropathic pain: An overview of the current treatment and future therapeutic approaches","volume":"33","author":"Cavalli","year":"2019","journal-title":"Int J Immunopathol Pharmacol"},{"key":"R3-20250821","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ejphar.2013.03.001","article-title":"Axonal voltage-gated ion channels as pharmacological targets for pain","volume":"708","author":"Moldovan","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"R4-20250821","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1146\/annurev.bi.64.070195.002425","article-title":"Structure and function of voltage-gated ion channels","volume":"64","author":"Catterall","year":"1995","journal-title":"Annu Rev Biochem"},{"key":"R5-20250821","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0006-3495(75)85842-5","article-title":"The receptor for tetrodotoxin and saxitoxin. 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