Kratom Science | 2021

Mitragynine / Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit ß-Arrestin-2

August 1, 2018

Natural products found in Mitragyna speciosa, commonly known as kratom, represent diverse scaffolds (indole, indolenine, and spiro pseudoindoxyl) with opioid activity, providing opportunities to better understand opioid pharmacology. Herein, we report the pharmacology and SAR studies both in vitro and in vivo of mitragynine pseudoindoxyl (3), an oxidative rearrangement product of the corynanthe alkaloid mitragynine. 3 and its corresponding corynantheidine analogs show promise as potent analgesics with a mechanism of action that includes mu opioid receptor agonism /delta opioid receptor antagonism. In vitro, 3 and its analogs were potent agonists in [35S]GTPγS assays at the mu opioid receptor but failed to recruit β-arrestin-2, which is associated with opioid side effects. Additionally, 3 developed analgesic tolerance more slowly than morphine, showed limited physical dependence, respiratory depression, constipation, and displayed no reward or aversion in CPP/CPA assays, suggesting that analogs might represent a promising new generation of novel pain relievers.

J. Med. Chem., 2016, 59 (18), pp 8381–8397

DOI: 10.1021/acs.jmedchem.6b00748

Publication Date (Web): August 24, 2016

Copyright © 2016 American Chemical Society

*Tel: 646-888-3669. E-mail: majumdas@mskcc.org.

Molecular Pharmacology and Chemistry Program and Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States

‡ Department of Pharmacodyanamics, University of Florida, Gainesville, Florida 032610, United States

§ Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, H-6726 Hungary

Source: https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00748#

Kratom Science | 2021 | kratom.com | info@kratom.com

New branding, same quality products

You'll be seeing quite a few changes within the Kratom.com brand, including an updated logo, packaging—and much more. We're celebrating 20 years in the industry and felt like it was time to freshen things up a bit. However, one thing that will always remain the same is the quality of our products. We'll always carry and supply the original Maeng Da™ and Bali Premium™—that we introduced to the market in 2001 as well as the service that you've come to expect. This is year come with some surprises that will go hand-in-hand with the new brand - for example, new value oriented savings opportunities for both consumers and our vendor and distributor partners, a NEW local Vendor Locator Map and or course a handful of exciting new products like our new Kratomade™ instant, flavored extracts and the first ever Salt-Based (SB-1™) extracts—two exciting game changers. As always, don't hesitate to reach out to us with any questions!

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