Strategy for making safer opioids bolstered

Majumdar, Susruta; Devi, Lakshmi A.

doi:10.1038/d41586-018-00045-1

NEWS AND VIEWS
15 January 2018
Correction 31 January 2018

Strategy for making safer opioids bolstered

Compounds have been made that activate only the G-protein signalling pathway when bound to the µ-opioid receptor — the target of opioid pain relievers. These compounds lack one of the main side effects of currently used opioids.

Susruta Majumdar⁰ &
Lakshmi A. Devi¹

Susruta Majumdar
1. Susruta Majumdar is in the Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
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Lakshmi A. Devi
1. Lakshmi A. Devi is in the Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
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Effective pain management is one of the greatest challenges of modern medicine. Opioids such as morphine and fentanyl are the preferred clinical treatments for moderate to severe pain because of their strong analgesic (pain-relieving) effects. But the ongoing epidemic of deaths from respiratory depression induced by opioid overdoses highlights the need for safer analgesics. Writing in Cell, Schmid et al.¹ report a series of compounds that provides a much-needed proof of principle of a strategy for making safer opioids.

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Nature 553, 286-288 (2018)

doi: https://doi.org/10.1038/d41586-018-00045-1

Updates & Corrections

Correction 31 January 2018: The article incorrectly stated that more than 100,000 adults suffer from chronic pain in the United States. The correct figure is more than 100 million adults.

References

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[1] Schmid, C. L. et al. Cell 171, 1165–1175 (2017).
Article PubMed CAS Google Scholar

[2] Institute of Medicine. Relieving Pain in America (Natl Acad. Press, 2011).
Google Scholar

[3] Pasternak, G. W. & Pan, Y.-X. Pharmacol. Rev. 65, 1257–1317 (2013).
Article PubMed CAS Google Scholar

[4] Grinnell, S. G. et al. Synapse 70, 395–407 (2016).
Article PubMed CAS Google Scholar

[5] Ananthan, S. AAPS J. 8, E118–E125 (2006).
Article PubMed CAS Google Scholar

[6] Eans, S. O. et al. J. Med. Chem. 58, 4905–4917 (2015).
Article PubMed CAS Google Scholar

[7] Spahn, V. et al. Science 355, 966–969 (2017).
Article PubMed CAS Google Scholar

[8] Fujita, W., Gomes, I. & Devi, L. A. Br. J. Pharmacol. 172, 375–387 (2015)
Article PubMed CAS Google Scholar

[9] Burford, N. T. et al. Proc. Natl Acad. Sci. USA 110, 10830–10835 (2013).
Article PubMed Google Scholar

[10] Rankovic, Z., Brust, T. F. & Bohn, L. M. Bioorg. Med. Chem. Lett. 26, 241–250 (2016).
Article PubMed CAS Google Scholar

[11] Bohn, L. M. et al. Science 286, 2495–2498 (1999).
Article PubMed CAS Google Scholar

[12] Bu, H., Liu, X., Tian, X., Yang, H. & Gao, F. Int. J. Neurosci. 125, 56–65 (2015).
Article PubMed CAS Google Scholar

[13] Li, Y. et al. Int. J. Mol. Sci. 10, 954–963 (2009).
Article PubMed CAS Google Scholar

[14] Raehal, K. M., Walker, J. K. & Bohn, L. M. J. Pharmacol. Exp. Ther. 314, 1195–1201 (2005).
Article PubMed CAS Google Scholar

[15] Harding, W. W. et al. J. Med. Chem. 48, 4765–4771 (2005).
Article PubMed CAS Google Scholar

[16] DeWire, S. M. et al. J. Pharmacol. Exp. Ther. 344, 708–717 (2013).
Article PubMed CAS Google Scholar

[17] Manglik, A. et al. Nature 537, 185–190 (2016).
Article PubMed CAS Google Scholar

[18] Kruegel, A. C. et al. J. Am. Chem. Soc. 138, 6754–6764 (2016).
Article PubMed CAS Google Scholar

[19] Váradi, A. et al. J. Med. Chem. 59, 8381–8397 (2016).
Article PubMed CAS Google Scholar

[20] Altarifi, A. A. et al. J. Psychopharmacol. 31, 730–739 (2017).
Article PubMed Google Scholar

Strategy for making safer opioids bolstered

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