Unexpected scaffold rearrangement product of pirenzepine found in commercial samples

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 commercial...

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Autores principales:	Marius Ozenil, Lukas Skos, Alexander Roller, Natalie Gajic, Wolfgang Holzer, Helmut Spreitzer, Sonja Platzer-Ozenil, Chrysoula Vraka, Marcus Hacker, Wolfgang Wadsak, Verena Pichler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af7948b51c254a38a9f2d2f540fc8bd3
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spelling	oai:doaj.org-article:af7948b51c254a38a9f2d2f540fc8bd32021-12-05T12:12:13ZUnexpected scaffold rearrangement product of pirenzepine found in commercial samples10.1038/s41598-021-02732-y2045-2322https://doaj.org/article/af7948b51c254a38a9f2d2f540fc8bd32021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02732-yhttps://doaj.org/toc/2045-2322Abstract 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.Marius OzenilLukas SkosAlexander RollerNatalie GajicWolfgang HolzerHelmut SpreitzerSonja Platzer-OzenilChrysoula VrakaMarcus HackerWolfgang WadsakVerena PichlerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marius Ozenil Lukas Skos Alexander Roller Natalie Gajic Wolfgang Holzer Helmut Spreitzer Sonja Platzer-Ozenil Chrysoula Vraka Marcus Hacker Wolfgang Wadsak Verena Pichler Unexpected scaffold rearrangement product of pirenzepine found in commercial samples
description	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.
format	article
author	Marius Ozenil Lukas Skos Alexander Roller Natalie Gajic Wolfgang Holzer Helmut Spreitzer Sonja Platzer-Ozenil Chrysoula Vraka Marcus Hacker Wolfgang Wadsak Verena Pichler
author_facet	Marius Ozenil Lukas Skos Alexander Roller Natalie Gajic Wolfgang Holzer Helmut Spreitzer Sonja Platzer-Ozenil Chrysoula Vraka Marcus Hacker Wolfgang Wadsak Verena Pichler
author_sort	Marius Ozenil
title	Unexpected scaffold rearrangement product of pirenzepine found in commercial samples
title_short	Unexpected scaffold rearrangement product of pirenzepine found in commercial samples
title_full	Unexpected scaffold rearrangement product of pirenzepine found in commercial samples
title_fullStr	Unexpected scaffold rearrangement product of pirenzepine found in commercial samples
title_full_unstemmed	Unexpected scaffold rearrangement product of pirenzepine found in commercial samples
title_sort	unexpected scaffold rearrangement product of pirenzepine found in commercial samples
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/af7948b51c254a38a9f2d2f540fc8bd3
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Unexpected scaffold rearrangement product of pirenzepine found in commercial samples

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