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| Other names | Spiro(2H-indole-2,1'(5'H)-indolizine)-7'-acetic acid, 6'-ethyl-1,2',3,3',6',7',8',8'a-octahydro-4-methoxy-alpha-(methoxymethylene)-3-oxo-, methyl ester, (alphaE,1'S,6'S,7'S,8'as)- |
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| Formula | C23H30N2O5 |
| Molar mass | 414.502 g·mol−1 |
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Mitragynine pseudoindoxyl is a rearrangement product of 7-hydroxymitragynine. It is an analgesic being more potent than morphine.
Pharmacology
Mitragynine pseudoindoxyl is a μ opioid receptor agonist and δ opioid receptor antagonist and acts as a G protein biased agonist at μ opioid receptors and possesses a favourable side effect profile compared to conventional opioids. Cryo-EM structures of μOR-Gi1 complex with mitragynine pseudoindoxyl and lofentanil (one of the most lethal opioids) revealed that the two ligands engage distinct subpockets, and molecular dynamics simulations showed additional differences in the binding site that promote distinct active-state conformations on the intracellular side of the receptor where G proteins and β-arrestins bind. Importantly, studies have shown that oxidative metabolism is capable of transforming mitragynine (the main alkaloid in kratom) into mitragynine pseudoindoxyl in two steps, which is likely to influence kratom’s complex pharmacological effects.
Chemistry
Mitragynine pseuodoindoxyl was first accessible via biomimetic semisynthesis from mitragynine. Total synthesis of an unnatural analogue was reported featuring an interrupted Ugi reaction as the key step. Scalable and modular total synthesis of the natural product has been also accomplished using a chiral pool based strategy. This study also demonstrated structural plasticity in biological systems.