Speciogynine at Serotonin Receptors (5-HT)

Full Ki matrix (assay-specific)

Summary: Speciogynine shows high-affinity binding at 5-HT₁A and 5-HT₂B in human receptor assays but does not activate 5-HT₂B in functional tests. The metabolite 9-O-desmethylspeciogynine converts this binding into 5-HT₁A agonism, likely explaining the in-vivo 5-HT₁A-like effects seen in rats. PMC

Receptor / Assay Ki_nM
5-HT1A (HEK, [3H]8‚ÄëOH‚ÄëDPAT) 38.5
5-HT1A (CHO, [3H]8‚ÄëOH‚ÄëDPAT) 95.5
5-HT2B (CHO, [125I]DOI) 23
5-HT2B (HEK, [3H]LSD) 108
5-HT7A (HEK, [3H]5‚ÄëCT) 1600
5-HT2A (HEK, [3H]LSD) 1320
5-HT2C (HEK, [3H]LSD) 5430

Functional activity (EC₅₀/IC₅₀, Emax/Imax notes)

Compound Target Potency Functional note
Speciogynine 5‑HT1A — No activation up to 30 μM
Speciogynine 5‑HT2B IC50 ≈ 2016 nM NInverse partial agonist; Imax ≈ 25% of SB206553
9‑O‑Desmethylspeciogynine 5‑HT1A EC50 ≈ 838 nM Full agonist; Emax ≈ 99–100% of 5‑HT
9‑O‑Desmethylspeciogynine 5‑HT2B IC50 ≈ 1472 nM Inverse partial agonist; Imax ≈ 45% of SB206553

Key Points

  • Binding assays: Radioligand competition shows tens-of-nanomolar affinity at 5-HT1A / 5-HT2B; weaker binding at 5-HT2A, 5-HT2C, and 5-HT7A. PMC
  • Functional: Parent compound shows no 5-HT2B agonism; 9-O-desmethylspeciogynine is a 5-HT1A agonist in vitro. PMC
  • Implication: Serotonergic contributions to kratom effects may be alkaloid-specific and metabolite-dependent, not simply “opioid-like”. PMC