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:
    • Mitragynine: predominant (~60–66% of total content)
    • Paynantheine: second-most abundant (~10–15%)
    • Speciogynine: ~7–9%
    • 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.

Unique Characteristics of Paynantheine

  • Unlike Mitragynine and 7-OH Mitragynine, functions as a competitive antagonist at opioid receptors — modulatory rather than primary psychoactive role.
  • Strong 5-HT₁A activity suggests potential mood-stabilizing and anxiolytic effects.
  • Its abundance ensures that, despite weaker activity, it contributes significantly to kratom’s overall balance of effects.

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 possibly 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/