Paynantheine Vs. Other Kratom Alkaloids

Comparative Analysis of Paynantheine with Other Kratom Alkaloids

  • Kratom’s pharmacology: Defined by its polyalkaloid composition, with over 40 indole alkaloids identified.
  • Key alkaloids: Mitragynine, 7-Hydroxymitragynine, Speciogynine, and Paynantheine are the most studied.
  • Alkaloid abundance:
    1. Mitragynine: predominant (~60–66% of total content)
    2. Paynantheine: second-most abundant (~10–15%)
    3. Speciogynine: ~7–9%
    4. 7-Hydroxymitragynine: <2%
  • Reference: ScienceDirect – Kratom Alkaloid Content [1]

Receptor Pharmacology Comparison

Alkaloid μ-Opioid Receptor (MOR) κ-Opioid Receptor (KOR) 5-HT₁A Receptor Notes
Mitragynine [2] Partial agonist Weak agonist Weak Strong analgesic effects
7-Hydroxymitragynine [3] Potent agonist Potent agonist Weak Most opioid-like, highest toxicity risk
Speciogynine [4] Minimal Minimal Weak Likely contributes to muscle relaxation
Paynantheine Antagonist Antagonist Strong (Ki ~32 nM) Non-opioid modulator, mood-related

Source: PMC – Kratom Alkaloid Pharmacology [5]

Safety & Toxicology Differences

  • 7-OH Mitragynine: Highest opioid toxicity, strong MOR agonism.
  • Mitragynine: Moderate toxicity, dose-dependent opioid risk.
  • Paynantheine: Minimal direct toxicity, weak/nonexistent opioid agonism — WHO Kratom Review [6].
  • Speciogynine: Limited data, low toxicity profile.

Paynantheine: Unique Pharmacological Profile

Unlike Mitragynine and 7-Hydroxymitragynine, Paynantheine functions primarily as a competitive antagonist at opioid receptors, offering a modulatory rather than a direct psychoactive effect. Its pharmacological profile also includes strong 5-HT₁A receptor activity, suggesting potential mood-stabilizing and anxiolytic benefits.

Contribution to Kratom’s Overall Effects

  1. Despite weaker receptor activity, its relative abundance in kratom ensures it significantly modulates the overall balance of effects.
  2. Acts in concert with Mitragynine and 7-OH Mitragynine to influence kratom’s complex pharmacology.

Summary

  • Mitragynine and 7-OH Mitragynine: Primary drivers of opioid-like effects.
  • Speciogynine: Likely involved in smooth muscle relaxation.
  • Paynantheine: A modulator with serotonergic and adrenergic effects, contributing to kratom’s polypharmacology and potentially mitigating opioid load.

Reference Link:

  1. Prozialeck, W. C., Jivan, J. K., & Andurkar, S. V. (2012). Pharmacology of Kratom: An emerging botanical agent with stimulant, analgesic, and opioid-like effects. Journal of the American Osteopathic Association, 112(12), 792–799. https://www.sciencedirect.com/science/article/pii/S0025619612600020
  2. Takayama, H. (2004). Chemistry and pharmacology of indole alkaloids from Mitragyna speciosa. Chemical & Pharmaceutical Bulletin, 52(8), 916–928. https://doi.org/10.1248/cpb.52.916
  3. Matsumoto, K., Horie, S., Ishikawa, H., Takayama, H., Aimi, N., Ponglux, D., & Watanabe, K. (2004). Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Sciences, 74(17), 2143–2155. https://doi.org/10.1016/j.lfs.2003.09.054
  4. 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. https://doi.org/10.1016/j.neuropharm.2017.08.026
  5. Ellis, C. R., Racz, R., Kruhlak, N. L., Kim, M. T., Zakharov, A. V., Southall, N., & Hawkins, E. G. (2020). Evaluating kratom alkaloids using PHASE: Opioid receptor binding of mitragynine, 7-hydroxymitragynine, and related compounds. PLOS ONE, 15(2), e0229646. https://doi.org/10.1371/journal.pone.0229646
  6. World Health Organization. (2021). Review of kratom and its alkaloids by the Expert Committee on Drug Dependence. WHO Technical Report. https://www.who.int/medicines/access/controlled-substances/ecdd_44_meeting/en/