Selected Grantee Publications
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Peripherally Mediated Opioid Combination Therapy in Mouse and Pig
Peterson et al., The Journal of Pain. 2025.
https://pubmed.ncbi.nlm.nih.gov/39542192
This study evaluates novel opioid combinations for pain relief with reduced side effects. Researchers investigated loperamide (a μ-opioid agonist) with either oxymorphindole or N‑benzyl-oxymorphindole—both δ-opioid receptor partial agonists—in mice (male and female) and pigs (male). These combinations produced synergistic analgesia across species without causing adverse effects or respiratory depression. The therapies significantly reduced hypersensitivity in post-injury models, outperforming morphine alone. These findings suggest that peripherally acting opioid combinations can offer effective, safer alternatives for pain management, potentially lowering opioid misuse and side effects. This approach could improve clinical strategies for treating chronic and acute pain with limited central opioid exposure. Supported by ORIP (T32OD010993), NHLBI, and NIDA.
A Multidimensional Metabolomics Workflow to Image Biodistribution and Evaluate Pharmacodynamics in Adult Zebrafish
Jackstadt et al., Disease Models & Mechanisms. 2022.
https://www.doi.org/10.1242/dmm.049550
The evaluation of tissue distribution and pharmacodynamic properties of a drug is essential but often expensive in clinical research. The investigators developed a multidimensional metabolomics platform to evaluate drug activity that integrates mass spectrometry–based imaging, absolute drug quantitation, in vivo isotope tracing, and global metabolome analysis in zebrafish. They validated this platform by evaluating whole-body distribution of the anti-rheumatic agent hydroxychloroquine sulfate and its impact on the systemic metabolism of adult zebrafish. This work suggests that the multidimensional metabolomics platform is a cost-effective method for evaluating on- and off-target effects of drugs. Supported by ORIP (R24OD024624) and NIEHS.