Speciociliatine Alkaloid Profile

At a glance

  • Speciociliatine (C₂₃H₃₀N₂O₄) — C3 epimer of mitragynine (3R vs 3S). CAS 14382-79-7, PubChem CID 15560576, FDA UNII M3NN8Z8ZJW.
  • Reported to be a partial μ-opioid receptor (MOR) agonist with higher MOR affinity than mitragynine in several assays; assay-dependent antagonist findings also exist (see Pharmacology).
  • In humans given a kratom product, speciociliatine showed the highest plasma exposure among measured alkaloids (AUC₀-inf ≈ 5120 nM·h), ~12× mitragynine, despite a lower dose in the product.
  • Key idea: Unlike mitragynine, speciogynine isn’t a μ-opioid agonist; its signal comes mainly from serotonergic interactions (notably 5-HT₁A/5-HT₂B), with in-vivo effects likely metabolite-driven (9-O-desmethylspeciogynine).

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    Pharmacology

  • Binding (human): MOR Kᵢ ≈ 116 ± 36 nM, KOR Kᵢ ≈ 54.5 ± 4.4 nM (radioligand binding; Obeng et al., as compiled in a 2022 Frontiers review). Kruegel et al. (2016) reported weak MOR antagonism and no measurable agonism in some functional assays → assay platform matters.
  • Function: Partial MOR agonism reported in several studies; no β-arrestin-2 recruitment noted in follow-ups cited by Kamble 2022.
  • In vivo (rodent): Antinociception ED₅₀ ≈ 6.25 mg/kg, comparable to morphine but weaker than 7-hydroxymitragynine (reviewed).

    • Embed here: Opioid Kᵢ chart → speciociliatine_Ki_opioid.png (with a caption noting sources and assay context).

    Pharmacokinetics (PK) & exposure

  • Rat PK (single-dose): 2.5 mg/kg i.v., 20 mg/kg p.o. → Vᵥ (Vz) ≈ 6.2 ± 2.3 L/kg, CL ≈ 0.7 ± 0.2 L/h/kg, Fₒ ≈ 20.7 % (UPLC-MS/MS NCA). (kₑ derived ≈ 0.113 h⁻¹ → t½ ≈ 6.1 h).
  • Human (kratom product): Speciociliatine AUC₀-inf ≈ 5120 nM·h vs mitragynine ≈ 420 nM·h in healthy volunteers; speciociliatine dose in product was ~¼ of mitragynine.

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    Metabolism & interactions

  • Dominant pathways: O-demethylation and mono-oxidation across species; no human-specific or disproportionate metabolites in HLM.
  • Enzymes: CYP3A4 predominant, CYP2D6 minor → potential sensitivity to strong CYP3A modulators in theory.
  • Hepatocyte stability (t½, 1 µM): mouse ~11 min; rat ~8 min; cynomolgus ~6.6 min; dog >120 min; human ~92 min.

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    Occurrence & analytics

  • Often 8–58% (w/w) of mitragynine levels in kratom tea/juice preps; typically ~1% of total alkaloid content in extracts (varies by chemotype)
  • Use LC-MS methods resolving diastereomer (mitragynine vs speciociliatine). Good identifiers: CAS 14382-79-7, CID 15560576.

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    Safety & caveats

  • Zebrafish embryo toxicity at very high in-vitro concentrations (>50 µg/mL) — likely above human plasma levels after oral kratom. Human clinical efficacy/safety data remain limited.

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    References

    • Kamble et al., 2022 / AAPS J (open) : Cross-species metabolism, enzymes, human exposure summary.
    • Berthold et al., 2021 / J Pharm Biomed Anal: Rat PK (i.v./p.o.) with validated UPLC-MS/MS.
    • Obeng et al., 2019/2021: Binding/efficacy datasets (compiled in Frontiers 2022 for quick access).
    • Frontiers reviews (2021/2022): ED₅₀ and dataset compilations + assay caveats.
    • PubChem / FDA GSRS : IDs, structure viewers.