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| Scientific reports. 2021 Dec 3. doi: 10.1038/s41598-021-02732-y. pii: 10.1038/s41598-021-02732-y |
| Unexpected scaffold rearrangement product of pirenzepine found in commercial samples. |
| Ozenil M1, Skos L2, Roller A3, Gajic N4, Holzer W5, Spreitzer H6, Platzer-Ozenil S7, Vraka C8, Hacker M9, Wadsak W10, Pichler V11 |
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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. |
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© 2021. The Author(s). |
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Publikations ID: 34862437 Quelle: öffnen |
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