{
  "abstract": "Background: Mislabeling of illicit drug products poses a serious risk to public health, especially in the rapidly evolving market for new psychoactive substances (NPS). Products sold as benzodiazepines may contain undisclosed novel synthetic opioids (NSOs), exposing opioid-naïve users to life-threatening respiratory depression.\n\nCase Report: A 34-year-old man ingested a pink tablet purchased online and labeled as “alprazolam triazolobenzophenone”, a ring-opened alprazolam prodrug, also known as “alprazafone”. Approximately 45 min after ingestion, he developed snoring and gasping respiration, hypoxemia and deep coma (Glasgow Coma Scale 3). Prehospital bag-valve ventilation and subsequent intubation resulted in prompt stabilization. The patient could be extubated 6 hours later. Contrary to the labeling, neither alprazolam nor its prodrug was detected in the tablet, blood or urine. Instead, the tablet contained approximately 1 mg of N-propionitrile chlorphine (cychlorphine), a piperidine benzimidazolone opioid of the emerging “orphine” class. Routine immunoassay screening for opioids and benzodiazepines was negative; identification required targeted LC-MS/MS. Six hours after ingestion, cychlorphine concentrations were 0.46 ng/mL in blood and 5.0 ng/mL in urine-to our knowledge the first human concentrations reported for this substance. In vitro, cychlorphine activated the µ-opioid receptor with an EC50 of 2.7 nM, i.e. 4.5-fold more potent than fentanyl (EC50 = 12.2 nM) within the same assay, with a binding affinity of Ki = 1.09 nM (fentanyl: Ki = 1.91 nM). The nitazene protonitazepyne was additionally detected in urine but not in blood or serum, indicating earlier intake and terminal elimination at the time of the event.\n\nConclusion: This case documents cychlorphine as a highly potent NSO capable of causing life-threatening respiratory depression at sub-nanogram-per-millilitre blood concentrations, and illustrates the specific danger of benzodiazepine products adulterated with opioids. No pharmacokinetic data are available for cychlorphine. The concentration, measured 6 hours post-intake, therefore likely underestimates peak exposure. Clinicians should consider NSO exposure in unexplained respiratory depression after NPS use, even where a benzodiazepine was expected. Accessible drug-checking services, take-home naloxone and NSO-capable confirmatory analysis are needed.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg , ,",
    "Poisons Information Center Freiburg, Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Center for Pediatrics, Medical Center – University of Freiburg, University of Freiburg , ,"
  ],
  "article_type": "case report",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
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        0
      ],
      "name": "Annette Zschiesche"
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    {
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      "name": "Johannes Nadler"
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    {
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        0
      ],
      "name": "Benedikt Pulver"
    },
    {
      "affs": [
        0
      ],
      "name": "Martin Scheu"
    },
    {
      "affs": [
        0
      ],
      "name": "Volker Auwärter"
    },
    {
      "affs": [
        1
      ],
      "name": "Maren Hermanns-Clausen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2dcncfpsrj6sa.bib",
  "cited_by": 0,
  "doi": "10.3389/ftox.2026.1951240",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730470/?tool=EBI",
  "id": "2dcncfpsrj6sa",
  "issns": [
    "2673-3080"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13730470",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Case Report"
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      "openalex",
      "3005|Forensic Toxicology and Drug Analysis"
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  "openalex": "W7223001002",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730470/pdf/?tool=EBI",
  "pmcid": "PMC13730470",
  "pmid": "42979587",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2dcncfpsrj6sa.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:46Z",
      "native_id": "PMC:PMC13730470",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13730470"
    },
    {
      "first_seen": "2026-11-07T12:23:01Z",
      "native_id": "PMC13730470",
      "source": "pmc",
      "url": "https://doi.org/10.3389/ftox.2026.1951240"
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  "subjects": [
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      "field": "medicine",
      "origin": "openalex:3005|Forensic Toxicology and Drug Analysis",
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  ],
  "title": "Case Report: Mislabeling of an online “alprazolam triazolobenzophenone” pill leads to severe intoxication with the novel synthetic opioid cychlorphine",
  "title_text": "Case Report: Mislabeling of an online “alprazolam triazolobenzophenone” pill leads to severe intoxication with the novel synthetic opioid cychlorphine",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:23:01Z",
  "url": "https://research.draconitic.com/paper/2dcncfpsrj6sa",
  "venue": "Frontiers in toxicology",
  "versions": []
}