Mitragynine Pseudoindoxyl

Mitragynine pseudoindoxyl is a derivative of mitragynine found in kratom, acting as a μ-opioid receptor agonist and δ-opioid receptor antagonist, with potential for pain relief due to its G protein-biased signaling that may lead to fewer side effects compared to traditional opioids. It is formed through the oxidative metabolism of mitragynine and exhibits greater analgesic potency than morphine, potentially influencing the complex effects of kratom.  

Key Characteristics

• Opioid Receptor Interactions:

  It acts as a μ-opioid receptor agonist, meaning it stimulates the receptor. It also acts as a δ-opioid receptor antagonist, blocking the receptor. 

• G Protein-Biased Agonism:

  It is a G protein-biased agonist at the μ-opioid receptor, a mechanism that could explain its potentially favorable side effect profile compared to conventional opioids. 

• Origin:

  It is a metabolic product of mitragynine, the main alkaloid in the plant kratom, created through oxidative metabolism. 

• Structural Differences:

• Cryo-EM structures show that mitragynine pseudoindoxyl engages different subpockets within the μ-opioid receptor compared to other potent opioids, leading to distinct active-state conformations that influence the binding of intracellular proteins.