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Paynantheine

PAY · CAS 639-48-5

Indole alkaloid

Formula

C₂₃H₃₀N₂O₄

Molecular Weight

398.5 g/mol

Abundance in Leaf

9–30%

Last Reviewed

2026-03-12

What Is Paynantheine?

Paynantheine is the second-most abundant alkaloid in kratom leaves, typically making up 9–30% of total alkaloid content. Unlike mitragynine, paynantheine has limited activity at opioid receptors. Its primary pharmacological action is smooth muscle relaxation — it relaxes the walls of blood vessels and the gastrointestinal tract. This mechanism is similar to the antispasmodic class of drugs and may contribute to some of kratom's non-opioid effects. Paynantheine also shows weak activity at serotonin and adrenergic receptors. Because it is present in high concentrations but does not strongly activate opioid pathways, paynantheine likely modulates the overall effect profile of whole-leaf kratom rather than driving its core analgesic effects. Research into paynantheine is ongoing, and its full contribution to kratom's pharmacology is not yet established.

Dose-Dependent Effects

Receptor Activity

Receptor	Ki (nM)	Activity Type	What This Means
Mu-opioid (MOR)	—	Weak / negligible	Very limited activity at the mu-opioid receptor. Paynantheine is not a significant contributor to kratom's opioid-like effects.
Smooth muscle	—	Relaxant	Relaxes vascular and gastrointestinal smooth muscle, similar to antispasmodic drugs. This is considered its primary pharmacological action.
Serotonin (5-HT receptors)	—	Weak affinity	Shows weak binding at several serotonin receptor subtypes. Clinical significance at concentrations found in whole-leaf kratom is unclear.

Safety & Adverse Effects

Research status

Paynantheine is an early-stage research compound with limited human pharmacokinetic data. As a smooth muscle relaxant present in high concentrations, it may contribute to the vasodilatory and gastrointestinal effects reported by kratom users.

Source: Kruegel & Grundmann 2018; Prozialeck et al. 2012

Drug Interactions

Antihypertensives and vasodilators

moderate

Theoretical additive blood pressure lowering due to smooth muscle relaxant properties. Clinical significance at typical kratom doses is not established.

CNS depressants (benzodiazepines, alcohol, opioids)

major

As a component of whole-leaf kratom, paynantheine is consumed alongside opioid-active alkaloids. Standard kratom interaction warnings apply.

View full interaction database

COA Connection

Appears on Certificates of Analysis as: PAY. Graded under Alkaloid Profile (Major component).

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Cited Literature

[1]

Kruegel AC, 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. ACS Chem Neurosci.

DOI: 10.1021/acschemneuro.7b00579

[2]

Prozialeck WC, Jivan JK, Andurkar SV (2012). Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc.

DOI: 10.7556/jaoa.2012.112.12.792

[3]

León F, Obeng S, Bhowmik S, et al. (2021). Activity of Mitragyna speciosa ("Kratom") alkaloids at serotonin receptors. J Med Chem.

DOI: 10.1016/j.ejphar.2021.174050

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