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. 2019 Feb 20;9:2405. doi: 10.1038/s41598-019-39555-x

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Convallatoxin is enhancer of morphine-mediated mu opioid receptor endocytosis. Convallatoxin could be a small-molecule, positive allosteric modulators for morphine-induced MOR endocytosis. Morphine binds to MOR and elicits antinociceptive effects. However, its poor ability to induce MOR endocytosis results in morphine tolerance after long-term use. Convallatoxin promotes better induction of receptor endocytosis by morphine, accompanied by better antinociception and reduced morphine tolerance.