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Currently, no systematic approach exists for evaluating these effects in whole-brain models, which typically focus on macroscopic phenomena, while pharmaceutical interventions operate at the molecular scale. Here we address this issue by presenting a computational approach for brain simulations using biophysically grounded mean-field models that integrate membrane conductances and synaptic receptors, showcased in the example of anesthesia. We show that anesthetics targeting GABA\n                    <jats:sub>A<\/jats:sub>\n                    and NMDA receptors can switch brain activity to generalized slow-wave patterns, as observed experimentally in deep anesthesia. To validate our models, we demonstrate that these slow-wave states exhibit reduced responsiveness to external stimuli and functional connectivity constrained by anatomical connectivity, mirroring experimental findings in anesthetized states across species. Our approach, founded on mean-field models that incorporate molecular realism, provides a robust framework for understanding how molecular-level drug actions impact whole-brain dynamics.\n                  <\/jats:p>","DOI":"10.1038\/s43588-025-00796-8","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T05:02:43Z","timestamp":1748408563000},"page":"405-417","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A computational approach to evaluate how molecular mechanisms impact large-scale brain activity"],"prefix":"10.1038","volume":"5","author":[{"given":"Maria","family":"Sacha","sequence":"first","affiliation":[]},{"given":"Federico","family":"Tesler","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7498-7122","authenticated-orcid":false,"given":"Rodrigo","family":"Cofre","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7405-0455","authenticated-orcid":false,"given":"Alain","family":"Destexhe","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"796_CR1","doi-asserted-by":"publisher","unstructured":"Arbabyazd, L. et al. 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