Speciogynine Alkaloid Profile

At a glance

  • Class: Corynanthe-type monoterpene indole alkaloid (MIA)
  • Formula: C₂₃H₃₀N₂O₄ · Stereochemistry: C-20 R (20R epimer of mitragynine)
  • CAS: 4697-67-0 · PubChem: (CID 15560577)
  • 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).

    • What it is & how it differs

    Speciogynine is a natural diastereomer of mitragynine found in Mitragyna speciosa (kratom). The single change at C-20 (20R vs 20S) shifts target engagement: speciogynine shows high-affinity binding at 5-HT₁A and 5-HT₂B but lacks the μ-opioid agonism associated with mitragynine.

    Receptor map

    Target What’s reported
    5-HT₁A High-affinity binding; parent speciogynine shows no agonism in vitro; its 9-O-desmethyl metabolite is a 5-HT₁A agonist.
    5-HT₂B High-affinity binding; parent shows no agonism (inverse partial activity only).
    Opioid (MOR/KOR/DOR) Speciogynine is not a MOR agonist under the same assay conditions tested for kratom alkaloids.

    In-vivo signals (rats)

    Speciogynine produced lower-lip retraction (a 5-HT₁A-linked behaviour) and antinociception in rats; both were blocked/attenuated by the 5-HT₁A antagonist WAY-100635, supporting a serotonergic mechanism via metabolites.

    Pharmacokinetics & exposure

  • i.v. (rats): single-dose PK reported for speciogynine (non-compartmental)

  • Oral (rats, kratom tea & a commercial shot): speciogynine showed low systemic exposure and was typically quantifiable only up to ~1 h post-dose, relative to better-exposed congeners.

    • Occurrence & product variability

    Quantitative work across plants/products shows substantial chemotype-to-chemotype variability in indole alkaloids (including speciogynine), underlining why labelled composition matters in retail products

    Biosynthesis & synthesis (for the chemistry readers)

  • Biosynthesis: the enzymes MsDCS1/2 and MsEnolMT control scaffold formation and the C-20 stereocentre, enabling directed biosynthesis of speciogynine (20R) vs mitragynine (20S).

  • Total synthesis: concise asymmetric routes to (+)-speciogynine have been published (helpful for standards and SAR work).