Development of Novel Blood Glucose-Lowering Dextromethorphan Derivatives That Do Not Affect the Brain

Peripherally Active Dextromethorphan Derivatives Lower Blood Glucose Levels by Targeting Pancreatic Islets. Cell Chemical Biology 2021

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Researchers have chemically modified the active ingredient dextromethorphan (DXM) so that it acts on the pancreatic islet cells and lowers blood glucose levels without affecting the central nervous system. The current results have now been published in Cell Chemical Biology.

The active ingredient dextromethorphan (DXM) is mainly known as a cough suppressant. Studies show that DXM also protects the islet cells of the pancreas and can lower blood glucose levels. However, the drug also affects the brain and can cause dizziness and fatigue. Researchers at the DZD partner German Diabetes Center (DDZ) have now succeeded in chemically modifying DXM in such a way that it no longer passes the blood-brain barrier, but nevertheless fully unfolds its positive effects.

The research team showed that the new DXM derivatives protect murine and human pancreatic islets from cell death. The derivatives also lower blood glucose levels without affecting the behavior of mice. The observation that the new compounds have significantly fewer side effects makes them interesting candidates for future diabetes therapy.

However, the findings may also be interesting for other applications: The active ingredient dextromethorphan is chemically related to morphine. These results show how DXM and possibly other morphinans can be chemically modified so that they have no side effects on the brain and still reach the peripheral tissue.

Original publication:
Scholz, O., Otter, S., Welters, A., Wörmeyer, L., Dolenšek, J., Klemen, S.M., Pohorec, V., Eberhard, D., Mrugala, J., Hamacher, A., Koch, A., Sanz, M., Hoffmann, T., Hogeback, J., Herebian, D., Klöcker, N., Piechot, A., Mayatepek, E., Lammert, E.: Peripherally active dextromethorphan derivatives lower blood glucose levels by targeting pancreatic islets. Cell Chemical Biology. 2021, 11 June, DOI: