An investigation into the formation of stable, protein-reactive and cytotoxic metabolites from tacrine in vitro

Autor:	Thomas F. Woolf, William F. Pool, S. Madden, B. Kevin Park
Rok vydání:	1993
Předmět:	Pharmacology biology Chemistry Metabolite Metabolism biology.organism_classification Biochemistry In vitro chemistry.chemical_compound Mechanism of action Microsoma Tacrine medicine Microsome medicine.symptom Cytotoxicity medicine.drug
Zdroj:	Biochemical Pharmacology. 46:13-20
ISSN:	0006-2952
Popis:	Tacrine (1,2,3,4-tetrahydro-9-aminoacridine hydrochloride; THA) is known to undergo extensive oxidative metabolism to a variety of mono- and dihydroxylated metabolites in animals and humans. The potential for tacrine to undergo metabolism to stable, protein-reactive and cytotoxic metabolites has been investigated in incubations with human and rat liver microsomes. Using lymphocytes as sensitive markers to quantify cytotoxicity, THA (50 μM) underwent NADPH-dependent bioactivation to a cytotoxic metabolite(s). NADPH-dependent cytotoxicity in the presence of rat and human micro-somes was 9.8 ± 3.1% (P
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::ad939665de74282a4f34fc983315a5c1 https://doi.org/10.1016/0006-2952(93)90342-t Zobrazit plný text záznamu