Definition
Mitragynine is an indole alkaloid derived from the corynantheine skeleton, found in the leaves of the Mitragyna speciosa tree. It is the quantitatively dominant component of the plant - typically making up 60-66 % of the total alkaloid content in the dry leaf. It was first isolated in 1921 by the British chemist Edmund Field at the Royal Botanic Gardens, Kew.
Chemical structure
Molecular formula: C23H30N2O4, molar mass 398.5 g/mol. Structurally it is a tetracyclic indole alkaloid with the 9-methoxy-corynantheidol configuration. Key structural features:
- an indole nucleus (benzene fused with pyrrole),
- a fused piperidine and tetrahydropyran ring,
- a methoxy group at carbon C9 (unlike the related yohimbine-type alkaloids),
- an ester group (methyl ester of a carboxylic acid) at position C16.
In the plant it occurs as a single stereoisomer (the natural (−)-mitragynine). Synthetic racemates have different physical properties.
Biosynthesis in the plant
Biosynthesis starts from the amino acid tryptophan, which is decarboxylated to tryptamine. This condenses with secologanin (a terpenoid aldehyde derived from geraniol) to form strictosidine - the common precursor of dozens of indole alkaloids in Rubiaceae and Apocynaceae. From strictosidine, a series of enzymatic steps (cytochrome P450, methyltransferases) leads to mitragynine.
This biosynthetic pathway is shared with alkaloids such as yohimbine or ajmalicine, which explains the structural similarities.
Mechanism at the molecular level
The scientific literature describes mitragynine as a partial agonist of the μ-opioid receptor (MOR) with signalling that differs from classical opioids: it preferentially activates the G-protein pathway and, to a lesser extent, the β-arrestin pathway. Mitragynine also shows affinity for the δ- and κ-opioid receptors and for adrenergic α2 receptors.
Note that this description corresponds to the results of in vitro and preclinical studies and serves solely to understand the compound's pharmacological profile - not as any recommendation for use.
Leaf content by origin and vein colour
The mitragynine content in the dry leaf varies according to origin, leaf age and processing method:
- Indonesia (Borneo, Sumatra): 0.8-1.5 % by weight (of which mitragynine 60-66 %).
- Malaysia: 0.5-1.1 %.
- Thailand (historical data): 0.3-1.0 %.
By vein colour, a higher mitragynine content is simplistically attributed to "white" and "green" leaves, with a relative shift towards 7-hydroxymitragynine in "red" fermented leaves. However, the variability between samples of the same designation is considerable.
Relationship to 7-hydroxymitragynine
Mitragynine undergoes oxidation, the product of which is 7-hydroxymitragynine - a structural analogue with a hydroxyl group at carbon C7. In in vitro tests this metabolite has an affinity for MOR several times higher than the parent compound, even though its content in the leaf does not exceed 2 % of the alkaloid profile.
Frequently asked questions
How does mitragynine differ from caffeine?
Structurally they are completely different classes: caffeine is a purine alkaloid (xanthine), mitragynine is an indole alkaloid derived from tryptamine. They also differ in their target receptors - caffeine acts on adenosine receptors, mitragynine mainly on opioid receptors.
What is the biological half-life of mitragynine?
Human studies (Trakulsrichai 2015) report an elimination half-life of approximately 9-24 hours, with large inter-individual variability determined by the metabolic enzymes CYP3A4 and CYP2D6.
When was mitragynine first isolated?
In 1921 by Edmund Field at the Royal Botanic Gardens, Kew (London). The structure was definitively confirmed by Zacharias et al. in 1965.
Is mitragynine regulated in the Czech Republic?
Yes. Since 2026, kratom and its main alkaloids fall under the category of psychomodulatory substances (PML) under the amendment to Act 167/1998 Coll.
References
- Field E. (1921). Mitragynine and mitraversine, two new alkaloids from species of Mitragyne. Journal of the Chemical Society, Transactions, 119, 887-891.
- Kruegel A. C., Grundmann O. (2018). The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse. Neuropharmacology, 134, 108-120.
- Trakulsrichai S. et al. (2015). Pharmacokinetics of mitragynine in man. Drug Design, Development and Therapy, 9, 2421-2429.
