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Virtual screening revealed stable binding modes between the investigated compounds (verapamil, cinnarizine, diltiazem, and flunarizine) and the 7SBF protein target, with cinnarizine exhibiting the most favorable interaction profile through strong hydrogen bonding with TYR-236 and GLN-124. Molecular dynamics simulations confirmed binding stability, particularly for cinnarizine, which maintained a root-mean-square deviation below 0.3 nm. Experimental validation via cAMP inhibition assays demonstrated significant MOR activation by all compounds, with cinnarizine showing superior potency (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 21.4 \u00b1 1.5 nM) and efficacy (Imax = 70% \u00b1 2%). The conserved MOR activation across structurally diverse CCBs supports a polypharmacological mechanism where these drugs concurrently modulate both calcium channels and opioid receptors. These findings not only elucidate a novel aspect of CCB pharmacology but also suggest new avenues for drug repurposing and the development of multi-target cardiovascular therapeutics.\n                  <\/jats:p>","DOI":"10.1177\/1540658x261442281","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T08:00:32Z","timestamp":1776499232000},"page":"431-443","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Mechanism of \u03bc-Opioid Receptor Activation"],"prefix":"10.1177","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0461-9526","authenticated-orcid":false,"given":"Yuhan","family":"Qu","sequence":"first","affiliation":[{"name":"Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuming","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Nanjing University of Chinese Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1736631"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.131568"},{"key":"e_1_3_5_4_2","first-page":"173","article-title":"Handling-Calcium-Channel","author":"Rudic B","year":"2025","unstructured":"Rudic B, , T\u00fcl\u00fcmen E, , Borggrefe MJAD. 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