Titel
Unexpected scaffold rearrangement product of pirenzepine found in commercial samples
Autor*in
Marius Ozenil
Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna
Lukas Skos
Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna
... show all
Abstract
Pharmacovigilance aims at a better understanding of the molecular events triggered by medications to prevent adverse effects, which despite significant advances in our analytical repertoire plague the use of drugs until today. In this study, we find that clinically prescribed and commercially available pirenzepine may not be the correct compound. Pirenzepine can undergo an unexpected scaffold rearrangement from the pharmaceutical active ingredient (API) to a previously uncharacterized benzimidazole. The rearrangement occurs under highly acidic conditions, which were believed to favour the dihydrochloride formation of pirenzepine. The rearranged products of pirenzepine and the structurally related telenzepine have significantly decreased affinity for the muscarinic acetylcholine receptor, the pharmacological target of these compounds. Fortunately, in situ rearrangement after oral application is no safety issue, as we show that reaction kinetics in gastric acid prevent rearrangement. The research community should consider appropriate measures to perform reliable receiving inspections in the commercial supply of well described and frequently used chemicals, in particular if experiments yield unexpected results.
Stichwort
Chemical safetyDrug safety
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
Scientific Reports
Band
11
ISSN
2045-2322
Erscheinungsdatum
2021
Publication
Springer Science and Business Media LLC
Erscheinungsdatum
2021
Zugänglichkeit
Rechte
Rechteangabe
© The Author(s) 2021
Universität Wien | Universitätsring 1 | 1010 Wien | T
+43-1-4277-0