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Neuropharmacology

Looking for inspiration in the opioid era

Nature Reviews Neuroscience volume 26, page 659 (2025)Cite this article

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In 1804, the German pharmacist Friedrich Sertürner first isolated an alkaloid from a poppy plant, which he called ‘morphium’ (morphine) after Morpheus — the Greek god of dreams. This opioid has been a godsend for treating individuals with severe pain. Now we dream of having an opioid analgesic that can be used in the clinic without fear of life-threatening respiratory depression and severe addiction, both potential adverse effects of these compounds.

The dangers of opioids extend beyond the clinic. In the USA, addiction to and abuse of the synthetic opioid fentanyl have become an epidemic, with illicit fentanyl overdosing causing ~84,000 deaths in 2023. Beyond the development of novel opioid analgesics themselves, the safety of their use could be improved by developing further opioid antagonists. One such antagonist, naloxone, can be used to mitigate the adverse effects of opioids, but its half-life is very short relative to opioids, making re-narcotization a serious concern. In addition, naloxone blocks opioid-mediated analgesia and does not lessen addiction but rather can worsen the withdrawal symptoms. As such, there remains a critical need to identify an alternative strategy that can maintain breathing selectively without compromising pain relief or exacerbating the risk of opioid addiction.

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References

Original article

  • Manzke, T. et al. 5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia. Science 301, 226–229 (2003)

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Related article

  • Peng, Y. J. et al. Activation of the carotid body by kappa opioid receptors mitigates fentanyl-induced respiratory depression. Function 6, zqaf020 (2005)

    Article  Google Scholar 

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Authors and Affiliations

  1. Manaaki Manawa — The Centre for Heart Research, Department of Physiology, Faculty of Health and Medical Sciences, University of Auckland, Grafton, New Zealand

    Olivia M. S. Gold

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  1. Olivia M. S. Gold
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Correspondence to Olivia M. S. Gold.

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The author declares no competing interests.

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Gold, O.M.S. Looking for inspiration in the opioid era. Nat. Rev. Neurosci. 26, 659 (2025). https://doi.org/10.1038/s41583-025-00963-w

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