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Rilmazafone: A designer benzodiazepine pro-drug involved in fatal intoxications.

Created on 23 Jun 2023

Authors

Robert Kronstrand, Markus Roman, Anna Johansson, Xiongyu Wu, Henrik Green, Michael T Truver

Published in

Journal of analytical toxicology. Jun 22, 2023. Epub Jun 22, 2023.

Abstract

Rilmazafone is a pro-drug that can be prescribed in Japan to treat insomnia. Rilmazafone metabolizes into active compounds by a ring closure resulting in a triazolo benzodiazepine structure similar to alprazolam. In mid-2022, the National Board of Forensic Medicine in Sweden were requested to investigate two separate deaths with the suspected use of pagoclone. Packages labelled "Pagoclone" were found at each scene that was suspected to contain rilmazafone based on website information. During screening by high resolution mass spectrometry, rilmazafone metabolites were presumptively identified. Due to the lack of reference material for the active metabolites, the metabolites were synthesized in house and quantification of the compounds identified in the two autopsy cases was prompted. In Case 1, femoral blood concentrations of 7.9, 65, and 170 ng/g of the metabolites rilmazolam, N-desmethyl rilmazolam and di-desmethyl rilmazolam, respectively, were detected. Additional toxicological findings included the medications haloperidol, alimemazine, fluoxetine, olanzapine, and acetaminophen. In Case 2, femoral blood concentrations of 1.7, 1.4 and 70 ng/g of rimazolam, N-desmethyl rilmazolam and di-desmethyl rilmazolam, respectively, were detected. Additional toxicological findings included loperamide, alimemazine, and pregabalin. The intake of rilmazafone was determined as the cause of death in Case 1 and contributed in the Case 2.

PMID:
37348041
Bibliographic data and abstract were imported from PubMed on 23 Jun 2023.

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