The authors of this paper discuss their examination of the in vitro μ-opioid receptor activation potential of three recently developed and structurally diverse, new synthetic opioids.
The emergence of structurally diverse, new synthetic opioids (NSOs) has caused the opioid crisis to spiral to new depths. Little information is available about the pharmacology of most novel opioids when they first emerge. In this paper, using a β-arrestin 2 recruitment assay, the authors report on their investigation of the in vitro μ-opioid receptor (MOR) activation potential of dipyanone, desmethylmoramide, and acetoxymethylketobemidone (O-AMKD) — recent NSOs that are structurally related to the prescription opioids methadone and ketobemidone. Their findings indicate that dipyanone is about equally active as methadone, whereas desmethylmoramide is considerably less active. A close structural analogue of ketobemidone and methylketobemidone, O-AMKD showed a lower potency and efficacy. Evaluation of the opioid substitution product buprenorphine and its metabolite norbuprenorphine confirmed the increased in vitro efficacy of the latter. In addition to in vitro characterization, this report details the first identification and full chemical analysis of dipyanone in a seized powder, as well as a postmortem toxicology case from the USA involving the drug. Dipyanone was quantified in blood, in which it was detected alongside other NSOs and novel benzodiazepines. Although dipyanone is currently not commonly encountered in forensic samples worldwide, its emergence is worrisome and representative of the dynamic NSO market. Publisher Abstract Provided