Document Detail


Identification of the urinary metabolites of tacrine in the rat.
MedLine Citation:
PMID:  1981736     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tacrine (THA) is a potent cholinesterase inhibitor being studied for the treatment of Alzheimer's disease. The metabolism and excretion of THA were studied in rats following a single oral dose of 20 mg/kg of THA. The results show THA was extensively metabolized in rats after oral administration. Three major urinary metabolites were isolated by HPLC on a semi-prep analytical phenyl column, and subsequent purification of the individual fractions on a semi-prep analytical cyano column. The major metabolic pathways involve the hydroxylation of the saturated ring at positions 1, 2, and 4. The structures of the metabolites 9-amino-1,2,3,4-tetrahydroacridin-1-ol (1-OH-THA), 9-amino-1,2,3,4-tetrahydroacridin-2-ol (2-OH-THA), and 9-amino-1,2,3,4-tetrahydroacridin-4-ol (4-OH-THA) were determined by electron impact mass spectrometry and/or 1H-NMR, and compared with synthetic references. The urinary excretion of THA and metabolites was quantitated by HPLC with UV detection. About 60% of the oral dose was eliminated as total THA, 1-OH-THA, 2-OH-THA, and 4-OH-THA over a 48-hr collection interval; and the non-conjugated THA and hydroxylated metabolites accounted for 45% of the dose.
Authors:
R S Hsu; G M Shutske; E M Dileo; S M Chesson; A R Linville; R C Allen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  18     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:    1990 Sep-Oct
Date Detail:
Created Date:  1991-04-25     Completed Date:  1991-04-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  779-83     Citation Subset:  IM    
Affiliation:
Chemical Research Department, Hoechst-Roussel Pharmaceuticals.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biotransformation
Chromatography, High Pressure Liquid
Hydroxylation
Magnetic Resonance Spectroscopy
Male
Mass Spectrometry
Rats
Rats, Inbred Strains
Reference Standards
Spectrophotometry, Ultraviolet
Tacrine / chemistry,  metabolism,  urine*
Chemical
Reg. No./Substance:
321-64-2/Tacrine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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