biostudies-literatureSerna CIntramural FDA HHS100064https://www.ebi.ac.uk/biostudies/studies/S-EPMC12856570biostudies-literatureUnknown1<h4>Background and purpose</h4>New approach methodologies (NAMs) including microphysiological systems in combination with human induced pluripotent stem cell (hiPSC)-derived neural cells and multielectrode array (MEA) have demonstrated utility for evaluating electrophysiological effects of CNS active compounds including those with potential seizurogenic liability. Here, we extend a neural NAM assay to assessment of an opioid agonist and reversal agent.<h4>Methods</h4>An in vitro human NAM composed of hiPSC-neurons and hiPSC-astrocytes coupled with MEA platform was used to assess spontaneous neural electrophysiology. Neural cells were cultured on MEA plates then treated with varying concentrations of the μ-opioid receptor agonist DAMGO (D-Ala(2)-mephe(4)-gly-ol(5))enkephalin). Following DAMNAM journalNonclinical human neural new approach methodologies (NAMs): Electrophysiological assessment of opioid agonist and antagonist combination.PMC12856570FD999999Bhardwaj BBlinova KSerna CFeaster TKfalseNonclinical human neural new approach methodologies (NAMs): Electrophysiological assessment of opioid agonist and antagonist combination.<h4>Background and purpose</h4>New approach methodologies (NAMs) including microphysiological systems in combination with human induced pluripotent stem cell (hiPSC)-derived neural cells and multielectrode array (MEA) have demonstrated utility for evaluating electrophysiological effects of CNS active compounds including those with potential seizurogenic liability. Here, we extend a neural NAM assay to assessment of an opioid agonist and reversal agent.<h4>Methods</h4>An in vitro human NAM composed of hiPSC-neurons and hiPSC-astrocytes coupled with MEA platform was used to assess spontaneous neural electrophysiology. Neural cells were cultured on MEA plates then treated with varying concentrations of the μ-opioid receptor agonist DAMGO (D-Ala(2)-mephe(4)-gly-ol(5))enkephalin). Following DAM2025-01-01T00:00:00Z2025 Oct2026-06-19T04:58:33.64Z2026-06-19T03:07:01.416ZS-EPMC128565704162530110.1016/j.namjnl.2025.100064