ArticleNAM journal2025
Nonclinical human neural new approach methodologies (NAMs): Electrophysiological assessment of opioid agonist and antagonist combination.
Article in NAM journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Advances in New Approach Methodologies at FDA's Division of Applied Regulatory Science.Clinical pharmacology and therapeutics · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Background and Purpose: 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. Methods: 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 DAMGO treatment, the opioid antagonist naloxone [10 μM] was added to each well to evaluate phenotypic reversal. Results: The opioid agonist DAMGO modulated neural electrophysiological activity in a concentration-dependent manner relative to vehicle control. These changes were observed across neural parameters relating to overall neural activity, single electrode burst, network burst, and synchronicity. These effects were reversed by the opioid antagonist naloxone. Moreover, DAMGO treatment disrupted higher order baseline neural patterns. Finally, subpopulation analysis revealed divergent opioid-induced higher order network response influenced by baseline network activity. Conclusions: These findings demonstrate the hiPSC neural NAM can characterize human network electrical activity at baseline and following exposure to an opioid agonist and antagonist pair. Future studies will investigate additional opioids and reversal agents, as well as other MEA metrics and activity patterns that may best describe concentration- and time-dependent changes in neural activity.
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Registered trials
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