{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T08:36:18Z","timestamp":1792917378385,"version":"4.5.0"},"reference-count":52,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Technology and Health Care"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Areca nut, a known carcinogen and addictive substance continues to be consumed globally. There is a lacuna in cessation strategies to combat areca-addiction. Xanomeline, a synthetic derivative of arecoline has gained significance in recent times for treatment of chronic neurological disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To conduct an\n                      <jats:italic toggle=\"yes\">in-silico<\/jats:italic>\n                      comparison between arecoline and xanomeline for identifying possible interactions that may unveil development of future intervention strategies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An integrative\n                      <jats:italic toggle=\"yes\">in-silico<\/jats:italic>\n                      approach was employed, including physicochemical profiling, toxicity prediction, molecular docking(MD), molecular dynamics simulation(MDS), and network pharmacology comparing arecoline and xanomeline. Docking was performed against muscarinic (CHRM1\u20135) and nicotinic (CHRNA3\/4\/7, CHRNB2\/4) receptor subtypes relevant to cholinergic signaling and addiction. MDS was used to assess protein ligand interactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Xanomeline demonstrated superior binding affinity across most cholinergic targets, particularly CHRM1 (\u20136.2\u2005kcal\/mol), compared with arecoline (\u20134.4\u2005kcal\/mol). Both ligands exhibited stable RMSD trajectories, although xanomeline complexes showed comparatively reduced RMSF fluctuations. Xanomeline demonstrated higher plasma-protein-binding (PPB) (61.72%) than arecoline (12.740%), higher probability of blood-brain-barrier (BBB) penetration (0.992\u2005cm\/s) than arecoline (0.89\u2005cm\/s). AMES toxicity showed moderate predicted mutagenic potential (0.625) for arecoline and low predicted mutagenic potential (0.024) for xanomeline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Within the limitations of this\n                      <jats:italic toggle=\"yes\">in-silico<\/jats:italic>\n                      investigation, xanomeline exhibited stronger binding affinity for addiction-related cholinergic receptors, improved stability in MDS, low predicted mutagenic potential and better CNS distribution characteristics than arecoline. These findings support the potential of xanomeline to modulate cholinergic pathways implicated in areca nut dependence and addiction and warrants further experimental validation as a promising pharmacological intervention strategy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09287329261490159","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:30:26Z","timestamp":1792589426000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioinformatics and network pharmacological characterization of xanomeline for therapeutic intervention in areca nut dependence"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7042-6435","authenticated-orcid":false,"given":"Divya","family":"Vinayachandran","sequence":"first","affiliation":[{"name":"SRM Kattankulathur Dental College and Hospital, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-3984","authenticated-orcid":false,"given":"Vivek","family":"Narayanan","sequence":"additional","affiliation":[{"name":"SRM Kattankulathur Dental College and Hospital, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1850-3581","authenticated-orcid":false,"given":"Saravana Karthikeyan","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"SRM Dental College, Ramapuram, Bharathi Salai, SRM Institute of Science and Technology, Chennai, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-043987"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/10826084.2020.1753772"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/add.15961"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.r1050"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/14659891.2024.2335486"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/10826084.2019.1686022"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/02537176221144711"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000018672"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1017\/S2045796020000384"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/10826084.2019.1666147"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00711"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnint.2025.1545260"},{"key":"e_1_3_3_14_2","first-page":"128","volume-title":"\u00a0Acrolein, Crotonaldehyde, and Arecoline.\u00a0","author":"IARC Working Group on the Identification of Carcinogenic Hazards to Humans.","unstructured":"IARC Working Group on the Identification of Carcinogenic Hazards to Humans.\u00a0Acrolein, Crotonaldehyde, and Arecoline.\u00a0Lyon (FR): International Agency for Research on Cancer; 2021. 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