Within the orphine / benzimidazolone class
- Brorphine — A structurally related orphine encountered as an illicit-market designer opioid. Reportedly causes significant respiratory depression and limited euphoria. Implicated in fatal overdoses.
- SR-14968 — A more potent SR-17018 analog from the Bohn lab. Produces respiratory depression at higher doses, but reversible by naloxone.
- SR-15098, SR-15099, SR-16435 — Additional research compounds in the same series; less characterized.
- Cychlorphine, spirochlorphine, spirobrorphine — Related orphine analogs detected in the unregulated drug supply[1].
Versus other "biased" or partial MOR agonists
- Oliceridine (TRV130, Olinvyk) — FDA-approved (2020) for IV use in moderate-to-severe acute pain in hospitalized patients. The first marketed biased MOR agonist. Still produces respiratory depression at clinical doses; whether its safety profile is meaningfully different from morphine remains debated.
- PZM21 — Designed as a biased MOR agonist; subsequent work showed it does cause respiratory depression and tolerance. Considered illustrative of the limits of the bias-as-safety hypothesis.
- Buprenorphine — Long-established partial MOR agonist (also a κ antagonist). FDA-approved for opioid use disorder and analgesia. Comparative pharmacology assays suggest SR-17018's intrinsic efficacy at MOR is similar to buprenorphine's, though the binding kinetics differ markedly.
Versus FDA-approved medications for opioid use disorder
| Methadone | Buprenorphine | Naltrexone (XR) | SR-17018 | |
|---|---|---|---|---|
| Regulatory status | Schedule II, FDA-approved | Schedule III, FDA-approved | Not scheduled, FDA-approved | Not approved; subject to U.S. Analogue Act risk |
| Mechanism | Full MOR agonist | Partial MOR agonist, κ antagonist | MOR antagonist | Atypical / partial MOR agonist |
| Human clinical trials | Decades, thousands of patients | Decades, thousands of patients | Multiple Phase III trials | None |
| Established efficacy in OUD | Yes | Yes | Yes (in selected patients) | Not established |
| Known adverse-event profile | Yes | Yes | Yes | Unknown |
Sources cited on this page
- [1]Public Alerts on Novel Synthetic Opioids — orphine analog series · Center for Forensic Science Research and Education (CFSRE) www.cfsre.org/nps-discovery/public-alerts
- [2]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