Opioid Pharmacology of Speciociliatine

Summary

Speciociliatine (C₂₃H₃₀N₂O₄) is the C-3 epimer of mitragynine (3R vs 3S) and exhibits moderate affinity for human μ- (MOR) and κ-opioid receptors (KOR). Across platforms, speciociliatine often behaves as a partial MOR agonist, although assay-dependent results have reported weak antagonism; interpretation should explicitly consider assay system and readout (G-protein vs β-arrestin). PMC+1

Binding (Kᵢ) at human opioid receptors

Radioligand binding (Eurofins Cerep; heterologous expression) found:

MOR (hMOP): Kᵢ = 54.5 ± 4.4 nM

KOR (hKOP): Kᵢ = 116 ± 36 nM (DOR/NOP not determined due to low displacement at 10 µM.)

Suggested figure to embed (category + this page):
Opioid Kᵢ bar chart (log scale):

speciociliatine_Ki_opioid_small.png (or SVG: speciociliatine_Ki_opioid.svg).

Functional activity (assay dependence)

G-protein assays (HTRF/others): Partial MOR agonism for speciociliatine; EC₅₀ ~39 nM for 7-OH-MG vs ~308 nM for mitragynine reported in the same study; speciociliatine displayed antinociception in rat hot-plate (iv) antagonized by naltrexone, consistent with opioid mediation.

BRET β-arrestin-2 recruitment: Earlier work reported no measurable MOR agonism and weak antagonism for speciociliatine (platform: BRET). Differences are plausibly due to assay choice and pathway bias.

Take-home

Speciociliatine reliably binds MOR and KOR in the 10–100 nM range (MOR favored).

Functional efficacy varies by assay; emphasize G-protein bias context and list the readout used whenever presenting activity claims.