What kind of compound it is
Its chemical family
The orphine family includes several research compounds (SR-14968, SR-15098, SR-15099, SR-16435) and the illicit-market opioid brorphine. CFSRE alerts have documented an expanding number of analogs detected in the unregulated drug supply[3].
Scientific deep diveMembers of the substituted piperidine benzimidazolone class
The shared scaffold is a piperidine ring substituted at two positions: one bearing a benzimidazolone ring system, the other a benzyl-type fragment. Variation across the family occurs at the benzimidazolone ring (chlorination patterns, propionitrile substitution) and at the second benzyl fragment.
- SR-14968 — more potent SR-17018 analog from the Bohn lab
- SR-15098, SR-15099, SR-16435 — research compounds, less characterized
- Brorphine — encountered in illicit market; implicated in fatal overdoses
- Chlorphine, cychlorphine, spirochlorphine, spirobrorphine — additional analogs identified by forensic labs
In some forensic alerts, SR-17018 has been reported under the name 5,6-dichloro desmethylchlorphine.
How it binds receptors
"Binding" is how tightly a drug sticks to its target receptor. Lower numbers (in nanomolar, nM) mean tighter binding. SR-17018 binds the μ-opioid receptor (MOR) tightly, the κ-opioid receptor moderately, and barely touches the δ-opioid receptor.
| Receptor | Ki | Relative affinity |
|---|---|---|
| μ-opioid receptor (MOR) | ~11 nM | High |
| κ-opioid receptor (KOR) | ~68 nM | Moderate |
| δ-opioid receptor (DOR) | >10,000 nM | Negligible |
How it behaves in cells
In test-tube assays of cells expressing the μ-opioid receptor, SR-17018 strongly activates G-protein signaling but barely recruits β-arrestin2. The ratio between these two is what drove its original characterization as a "highly biased" agonist.
Scientific deep diveIn-vitro functional activity at MOR
| Assay | EC50 | Emax |
|---|---|---|
| GTPγS binding (G-protein activation) | ~97–193 nM | ~72–75% |
| cAMP accumulation (G-protein signaling) | ~76 nM | ~105% |
| β-arrestin2 recruitment | >10,000 nM | ~10% |
The very large gap between G-protein and β-arrestin EC50 values is the basis for SR-17018's original characterization as a "highly biased" MOR agonist[1]. This characterization has since been challenged — see Mechanism of action.
Physical properties
SR-17018 is practically insoluble in water and propylene glycol. It dissolves reasonably well in organic solvents. These properties effectively limit it to oral administration — it cannot be efficiently insufflated, smoked, or injected.
- Practically insoluble in water and propylene glycol
- Soluble in DMSO and PEG300
- Soluble in 10:10:80 DMSO / Tween-80 / water mixtures (community-formulated oral suspensions)
Sources cited on this page
- [1]Schmid CL, Kennedy NM, Ross NC, Lovell KM, Yue Z, Morgenweck J, Cameron MD, Bannister TD, Bohn LM. Bias factor and therapeutic window correlate to predict safer opioid analgesics · Cell, 171(5):1165–1175.e13 (2017) doi.org/10.1016/j.cell.2017.10.035
- [2]SR-17018 — Wikipedia · Wikipedia en.wikipedia.org/wiki/SR-17018 — Useful index of primary literature
- [3]Public Alerts on Novel Synthetic Opioids — orphine analog series · Center for Forensic Science Research and Education (CFSRE) www.cfsre.org/nps-discovery/public-alerts