Nonclinical human neural new approach methodologies (NAMs): Electrophysiological assessment of opioid agonist and antagonist combination

Authors: Carlos Serna III, Bhavya Bhardwaj, Tromondae K. Feaster, and Ksenia Blinova

NAM Journal, 22 October 2025

Using a human-relevant NAMs model on Maestro Pro MEA, researchers explored how opioids influence brain activity. 

Understanding how opioids alter brain activity is key to developing safer pain treatments and reversal agents. In this study, researchers examined how an opioid receptor agonist and its competitive antagonist affect neural signaling in a human-relevant in vitro model—a critical step toward advancing New Approach Methodologies (NAMs) that reduce reliance on animal testing. 

Using Axion BioSystems’ hands-free Maestro Pro platform, the team recorded changes in spontaneous firing, synchronous activity, and overall network dynamics in vitro, with no labels, dyes, or complicated steps. Findings showed that the opioid agonist produced an increase in individual neuronal spiking but a decrease in coordinated network bursting, effects that were reversed by the antagonist. 

These results demonstrate how high-throughput, human cell–based electrophysiology can reveal complex network-level drug responses. Studies like this underscore the promise of Maestro-based NAMs as powerful tools for evaluating neural safety and pharmacology in vitro