Paynantheine: Pharmacological Profile

Pharmacological Profile Of Paynantheine

Paynantheine [1] is among the most studied “minor” Kratom alkaloids due to its relatively high abundance and distinct receptor activity. Unlike Mitragynine or 7-Hydroxymitragynine, which act as opioid receptor agonists, Paynantheine demonstrates a unique profile combining opioid receptor antagonism with serotonin receptor modulation. This section explores its chemical identity, occurrence, analytical detection, and receptor binding data, providing a foundation for understanding its pharmacological role.

Chemical Identity & Structure

Alkaloid class: Paynantheine is classified as an indole alkaloid found in Mitragyna speciosa, ACS Journal of Natural Products [2].
Molecular formula: C₂₃H₂₈N₂O₅ [3], with a molecular weight of ~408.48 g/mol.
Structural features: Contains a core indole framework and methoxy substitutions, contributing to receptor-binding properties. ResearchGate – Chemical Structures of Kratom Alkaloids.

Together, these properties position Paynantheine as a chemically distinct alkaloid with potential pharmacological relevance.

Occurrence in Kratom Leaves

Paynantheine is the second-most abundant alkaloid in kratom leaves, typically accounting for 10–15% of total alkaloid content [4]. The concentration varies depending on strain type, maturity stage, and drying methods. Total alkaloid content in dried leaves usually ranges from 0.5–1.5% of leaf mass, ScienceDirect – Kratom Alkaloid Content [5].

Alkaloid Composition in Kratom Leaves

Alkaloid	Approx. % of Total Alkaloids
Mitragynine	~66%
Paynantheine	~10–15%
Speciogynine	~7%

Analytical Detection Methods

Quantification of Paynantheine in Mitragyna speciosa leaves is typically performed using High-Performance Liquid Chromatography (HPLC) with UV detection at 225 nm or Liquid Chromatography–Mass Spectrometry (LC–MS/MS) in positive electrospray ionization mode [6, 7]. Standard conditions reported include a C18 reversed-phase column (250 × 4.6 mm, 5 µm particle size), with a mobile phase of acetonitrile and 0.1% formic acid in water (gradient elution, 30–70% acetonitrile over 20 minutes) [8].
Detection limits for Paynantheine are typically in the low nanogram per milliliter (ng/mL) range, making these methods suitable for both plant extract analysis and biological samples [9].
Reference standards are used to ensure quantitation accuracy, and published LC–MS methods confirm the reproducibility of retention times and fragmentation patterns [10].

Receptor Binding & Mechanisms

A. Serotonin Receptor Affinity

In vitro studies demonstrate selective serotonergic activity:

Receptor	Paynantheine K_i (nM)	Notes
5-HT₁A	~32 nM	High affinity [11]
5-HT₂B	<100 nM	Moderate binding [12]
5-HT₂A	~815 nM	Lower affinity [13]
5-HT₇	~870 nM	Relatively weak binding [14]

B. Opioid Receptor Interaction

Functions as a competitive antagonist at μ-opioid receptors (MOR) and κ-opioid receptors (KOR) — PMC – Pharmacological Characterization [15].
Does not act as an agonist, unlike Mitragynine or 7-OH Mitragynine.

This suggests Paynantheine may modulate kratom’s overall pharmacology by balancing opioid receptor effects with serotonergic activity.

Summary

Identity: Indole alkaloid, molecular weight 408.48 g/mol.
Abundance: 10–15% of total alkaloids in kratom leaves.
Detection: HPLC and LC–MS validated with reference standards.
Pharmacology: Strong affinity for 5-HT₁A and 5-HT₂B receptors; antagonist at MOR and KOR.
Implication: Likely contributes to mood-modulating and modulatory effects of kratom but not primary analgesia.