Case Report: Mislabeling of an online “alprazolam triazolobenzophenone” pill leads to severe intoxication with the novel synthetic opioid cychlorphine
- 1Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg , ,
- 2Poisons 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 , ,
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.
Case 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.
Conclusion: 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.
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BibTeX
@article{zschiesche2026case,
title = {{Case Report: Mislabeling of an online “alprazolam triazolobenzophenone” pill leads to severe intoxication with the novel synthetic opioid cychlorphine}},
author = {Annette Zschiesche and Johannes Nadler and Benedikt Pulver and Martin Scheu and Volker Auwärter and Maren Hermanns-Clausen},
journal = {Frontiers in toxicology},
year = {2026},
month = oct,
doi = {10.3389/ftox.2026.1951240},
url = {https://europepmc.org/article/PMC/PMC13730470},
note = {CC BY},
}
RIS
TY - JOUR
TI - Case Report: Mislabeling of an online “alprazolam triazolobenzophenone” pill leads to severe intoxication with the novel synthetic opioid cychlorphine
AU - Annette Zschiesche
AU - Johannes Nadler
AU - Benedikt Pulver
AU - Martin Scheu
AU - Volker Auwärter
AU - Maren Hermanns-Clausen
PY - 2026
DA - 2026/10/21
JO - Frontiers in toxicology
DO - 10.3389/ftox.2026.1951240
UR - https://europepmc.org/article/PMC/PMC13730470
AB - 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. Case 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. Conclusion: 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.
SN - 2673-3080
ER -