Structure, modification, and µ-opioid receptor binding — comparing classical opioids to kratom's alkaloids and their synthetic derivatives.

The classical opioids (morphine, codeine) and the kratom-derived alkaloids (mitragynine, 7-OH, MGM-15, pseudoindoxyl) hit the same receptor — but their structures, binding profiles, and what happens when you modify them in a lab are different in ways that matter for how dependence develops and how withdrawal behaves.

This page lines them up side-by-side: structure, key modifications, µ-opioid receptor binding affinity, agonist behavior, and what each modification does. It’s the molecular-level counterpart to the compound overviews in the Compounds section.

Pharmacological & Structural Comparison — µ-Opioid Receptor Ligands

Morphine vs. Mitragyna Alkaloids: Structure, Modification & µ-Opioid Receptor Binding

A side-by-side look at morphine and six kratom-derived indole alkaloids — how small structural changes (hydroxylation, acetylation, double-bond reduction, oxidation) shift binding affinity and pharmacology at the µ-opioid receptor.

Structural map — how each modification reshapes µ-opioid receptor binding

Every kratom alkaloid in this chart is a structural modification of mitragynine. Bars show approximate relative µ-opioid receptor affinity (not absolute Kᵢ). Reduction steps (+ H₂, purple) consistently raise affinity — saturating a double bond adds conformational flexibility for a tighter receptor fit. Morphine is not shown: it is a phenanthrene-class opioid, not a structural derivative of mitragynine.

General trend in µ-opioid receptor binding — affinity / potency

← Lower affinity / potencyHigher affinity / potency →

Mitragynine

low–moderate

Kᵢ ≈ 80–200 nM

›

Dihydro-mitragynine (DHM)

moderate

Kᵢ ≈ 10–30 nM

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Pseudoindoxyl mitragynine

moderate–high

Kᵢ ≈ 0.2–1 nM

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Morphine

high; reference

Kᵢ ≈ 1.0 nM

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7-Acetoxymitragynine

moderate–high

Kᵢ not established

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7-Hydroxymitragynine

very high

Kᵢ ≈ 0.2–0.6 nM

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Dihydro-7-hydroxymitragynine (MGM-15)

very high

Kᵢ ≈ 0.03–0.2 nM

Potency rankings vary by species and by the outcome measured (receptor binding, analgesia, behavioral models, etc.).

Morphine

7-Hydroxymitragynine

7-Acetoxymitragynine

Dihydro-7-hydroxymitragynine

also known as MGM-15

Mitragynine

Dihydro-mitragynine

often sold as DHM or MIT-A

Pseudoindoxyl mitragynine

Molecule

Molecular information

neutral / free base

Molecular formulaC₁₇H₁₉NO₃

Molecular weight285.34 g/mol

Naturally occurring opioid alkaloid (phenanthrene class)

Molecular formulaC₂₃H₃₀N₂O₅

Molecular weight414.50 g/mol

Naturally occurring indole alkaloid

Molecular formulaC₂₅H₃₂N₂O₆

Molecular weight456.54 g/mol

Semi-synthetic acetate ester of 7-hydroxymitragynine

Molecular formulaC₂₃H₃₂N₂O₅

Molecular weight416.52 g/mol

1,2-dihydro derivative of 7-hydroxymitragynine (MGM-15)

Molecular formulaC₂₃H₃₀N₂O₄

Molecular weight398.50 g/mol

Naturally occurring indole alkaloid

Molecular formulaC₂₃H₃₂N₂O₄

Molecular weight400.51 g/mol

Hydrogenated derivative of mitragynine — a loosely-defined market product

Molecular formulaC₂₃H₃₀N₂O₅

Molecular weight414.50 g/mol

Oxidized analog of mitragynine (indoxyl alkaloid)

Key structural differences

compared to mitragynine

Phenanthrene core (3 fused rings)
Two phenolic hydroxyl groups (3- and 6-)
Ether bridge (O) between rings (4,5-epoxy)
Tertiary amine (N–CH₃)
No methoxy group
Different ring system than indole alkaloids

Hydroxyl group at 7-position (–OH)
Methoxy group (–OCH₃) at 9-position
Double bond in the side ring
Tertiary amine (N–CH₃)

Acetate ester (–O–C(=O)CH₃) at the 7-position
Otherwise the same core as 7-hydroxymitragynine
Methoxy group (–OCH₃) at 9-position
Double bond in the side ring; tertiary amine (N–CH₃)

The indolenine C=N of 7-hydroxymitragynine is reduced to a C–N single bond (1,2-dihydro)
7-Hydroxyindolenine → 7-hydroxyindoline; one new sp³ stereocentre
Methoxyacrylate side chain unchanged; +2 hydrogen atoms

No hydroxyl group at 7-position
Methoxy group (–OCH₃) at 9-position
Double bond in the side ring
Tertiary amine (N–CH₃)

Same core as mitragynine
Side-ring double bond is reduced (saturated)
+2 hydrogen atoms

Oxidation of the indole to an indoxyl (C=O at 3-position)
Methoxy group (–OCH₃) at 9-position
Double bond in the side ring
Tertiary amine (N–CH₃)

Effects & potency

general profiles

Strong µ-opioid agonist
High analgesia, euphoria
Sedation, respiratory depression
High abuse liability

Potency (analgesia): High (reference opioid)

Partial µ-opioid agonist — very high affinity and potency, but low intrinsic efficacy (does not fully activate the receptor)
Potent analgesic in animal models, despite only partially activating the receptor
Less sedation / respiratory depression than morphine (in some studies)

Potency (analgesia): Very high — but a partial agonist (low intrinsic efficacy)

µ-opioid agonist (semi-synthetic derivative)
Retains opioid activity, but reported less potent than 7-hydroxymitragynine
Acetate ester — hydrolyzed to 7-hydroxymitragynine in vivo, so it acts partly as a precursor

Potency (analgesia): Moderate to high (below 7-hydroxymitragynine)

More potent µ- and δ-opioid agonist than 7-hydroxymitragynine (animal data)
More sedation and respiratory depression than 7-hydroxymitragynine
Sold as a designer drug since early 2025; its 9-fluoro analog (MGM-16) is more potent still

Potency (analgesia): Very high (> 7-hydroxymitragynine in studies)

Partial µ-opioid agonist
Mild to moderate analgesia
Stimulating, mood-lifting, anxiolytic
Lower sedation and respiratory depression

Potency (analgesia): Low to moderate

µ-opioid agonist (partial to moderate)
More analgesic and sedating than mitragynine
Lower potency than 7-hydroxymitragynine and dihydro-7-hydroxymitragynine

Potency (analgesia): Moderate

µ-opioid agonist (partial to moderate)
Analgesic, sedating
Potency reported between mitragynine and 7-hydroxymitragynine in some studies

Potency (analgesia): Moderate to high (variable reports)

Binding affinity

µ-opioid receptor · lower Kᵢ = higher affinity

Kᵢ ≈ 1.0 nM

Reference · high affinity

Kᵢ ≈ 0.2 – 0.6 nM

~2–5× higher affinity than morphine

Kᵢ — not established

Retains µ-opioid activity; reported less potent than 7-OH. Hydrolyzed to 7-OH in vivo.

Kᵢ ≈ 0.03 – 0.2 nM

~5–30× higher affinity than morphine

Kᵢ ≈ 80 – 200 nM

~80–200× lower affinity than morphine

Kᵢ ≈ 10 – 30 nM

~10–30× lower affinity than morphine

Kᵢ ≈ 0.2 – 1 nM

~1–5× higher affinity than morphine

Elimination half-life

approx. plasma t½ · how long it lasts in the body

≈ 2 – 4 h

Plasma elimination t½; well characterized. ~Half cleared by ~3 h, ~95% by ~15–18 h.

≈ 2.5 – 3 h

Human single-dose plasma t½. ~Half cleared by ~3 h, ~95% by ~12–15 h.

est. Brief (ester)

Not directly measured. As an acetate ester it is expected to be rapidly cleaved by esterases to 7-hydroxymitragynine in vivo — the intact ester is unlikely to persist.

est. ≈ 5 – 14 h

Estimated by analogy to 7-hydroxymitragynine (MGM-15) — no human PK data. Reducing the indolenine raises lipophilicity, biasing toward a longer washout than the parent.

≈ 3 – 24 h

Reported human t½ varies widely with study & preparation — from a few hours up to ~1 day.

est. ≈ 10 – 30 h

Estimated by analogy to mitragynine — no human PK data. The saturated (hydrogenated) analog is more lipophilic, biasing toward a longer terminal half-life.

est. ≈ 4 – 12 h

Estimated by analogy to 7-hydroxymitragynine — no human PK data. Oxidative rearrangement product; washout not directly measured.

* Effects vary by species, dose, individual physiology, and route of administration. † Kᵢ (inhibition constant) values are approximate ranges compiled from peer-reviewed in vitro radioligand binding studies at the µ-opioid receptor; a lower Kᵢ indicates higher binding affinity.

Key structural features & their role in receptor binding

Hydroxyl (–OH)

Hydrogen bonding with receptor amino acids — increases affinity.

OCH₃

Methoxy (–OCH₃)

Raises lipophilicity; enhances binding via hydrophobic interactions.

C=C

Double bond

Increases rigidity and planarity — aids π–π stacking and positioning.

–CH₂–CH₂–

Reduced bond

Adds flexibility; allows better 3D fit and more van der Waals contacts.

Carbonyl (indoxyl)

Strong hydrogen-bond acceptor; raises electrophilicity and binding potential.

N–CH₃

Tertiary amine

Forms ionic interactions with aspartate residues in the receptor.

Consumer caution — labels & lab results are frequently unreliable

These semi-synthetic alkaloids are sold online, in smoke shops and in gas stations with minimal oversight. Certificates of analysis (“COAs” / lab results) supplied with such products are frequently missing, outdated, or fabricated, and independent forensic testing repeatedly finds products mislabeled. A product sold under one name — say “MIT-A” — may actually contain a different alkaloid (such as MGM-15 or 7-OH), a different concentration than stated, or an undisclosed mixture. The name, the potency figure, and the lab paperwork on a package cannot be assumed to reflect what is actually inside.

Notes

All molecular formulas and weights are for the neutral (free-base) form.
Formulas & weights independently verified against PubChem and FDA / EU Drugs Agency references.
π–π stacking: an attractive interaction between the flat, electron-rich faces of two aromatic rings — here, the alkaloid’s indole ring and aromatic residues (Phe / Tyr / Trp) lining the receptor pocket. Flatter, more rigid molecules stack more effectively.
Half-lives marked est. are structure-based extrapolations, not measured data — no human pharmacokinetic studies exist for those analogs.
Effect profiles are general summaries; individual responses vary. This chart is for educational and scientific reference only.

Sources (selected)

Kruegel AC, Grundmann O. The medicinal chemistry & neuropharmacology of kratom. Neuropharmacology, 2018.
Matsumoto K, et al. Opioid receptor binding profiles of mitragynine alkaloids. Bioorg. Med. Chem. Lett.
Váradi A, et al. Mitragynine / oxidized analogs at the µ-opioid receptor. PLoS One, 2017.
Takayama H, et al. In vitro evaluation of kratom alkaloids on opioid receptors. Life Sci., 2010.
PubChem Compound Database (NIH) — CIDs 5288826, 44301524, 44301701, 3034396.

About this chart

Molecular structures rendered from verified canonical SMILES / InChI; every database-listed compound was confirmed by InChIKey match. Indole alkaloid numbering follows standard Mitragyna convention.

MGM-15 is the 1,2-dihydro derivative of 7-hydroxymitragynine (the indolenine C=N is reduced); first reported 2014, sold as a designer drug since 2025. “Dihydro-mitragynine / DHM” is a loosely-defined hydrogenated market product. Mitragynine pseudoindoxyl is an oxidative rearrangement of 7-hydroxymitragynine, isomeric with it.

Reference compiled — structures & data verified 2024

🩺 Reference, not advice. This is structural pharmacology. It won’t tell you what to take or how to taper — those decisions belong with a clinician familiar with your situation.