Literature DB >> 15726887

Human hepatic metabolism of the anxiolytic agent, RWJ-51521--API-MS/MS identification of metabolites.

W N Wu1, L A McKown, A B Reitz.   

Abstract

The In vitro metabolism of the anxiolytic agent, RWJ-51521 was conducted after incubation with human hepatic S9 fraction in the presence of an NADPH-generating system. Unchanged RWJ-51521 (30% of the sample) and a total of 11 metabolites were profiled, quantified, and tentatively identified on the basis of API (ionspray)-MS/MS data. The 4 proposed metabolic pathways for RWJ-51521 are: (1) N/O-dealkylation, (2) phenylhydroxylation, (3) pyrido-oxidation, and (4) dehydration. Pathway 1 formed 2 major and 3 minor N/O-desalkyl metabolites (M1 &amp; M3, 50%) and in conjunction with pathway 4, formed 2 moderate dehydrated metabolites (M4 &amp; M5, 14%). Pathways 2 and 3 alone, and in conjunction with pathway 4, produced 4 minor metabolites (each < or =2%). RWJ-51521 is extensively metabolized in human hepatic S9 fraction.

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Year:  2004        PMID： 15726887     DOI： 10.1007/BF03190608

Source DB:  PubMed          Journal:  Eur J Drug Metab Pharmacokinet        ISSN： 0378-7966            Impact factor:   2.441


  7 in total

1.  Potential anxiolytic agents. Pyrido[1,2-a]benzimidazoles: a new structural class of ligands for the benzodiazepine binding site on GABA-A receptors.

Authors:  B E Maryanoff; W Ho; D F McComsey; A B Reitz; P P Grous; S O Nortey; R P Shank; B Dubinsky; R J Taylor; J F Gardocki
Journal:  J Med Chem       Date:  1995-01-06       Impact factor: 7.446

2.  Potential anxiolytic agents. 3. Novel A-ring modified pyrido[1,2-a]benzimidazoles.

Authors:  B E Maryanoff; S O Nortey; J J McNally; P J Sanfilippo; D F McComsey; B Dubinsky; R P Shank; A B Reitz
Journal:  Bioorg Med Chem Lett       Date:  1999-06-07       Impact factor: 2.823

3.  5-ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydrobenzo[4,5]imidazo[1,2a]pyridine-4-N-(2-fluorophenyl)carboxamide (RWJ-51204), a new nonbenzodiazepine anxiolytic.

Authors:  Barry Dubinsky; Anil H Vaidya; Daniel I Rosenthal; Coralie Hochman; Jeffrey J Crooke; Samantha DeLuca; Ann DeVine; Cathy T Cheo-Isaacs; Alexandre R Carter; Alfonzo D Jordan; Allen B Reitz; Richard P Shank
Journal:  J Pharmacol Exp Ther       Date:  2002-11       Impact factor: 4.030

Review 4.  New directions in anxiolytic drug research.

Authors:  M K Scott; D A Demeter; S O Nortey; B Dubinsky; R P Shank; A B Reitz
Journal:  Prog Med Chem       Date:  1999

5.  Potential anxiolytic agents. Part 4: novel orally-active N(5)-substituted pyrido[1,2-a]benzimidazoles with high GABA-A receptor affinity.

Authors:  Alfonzo D Jordan; Anil H Vaidya; Daniel I Rosenthal; Barry Dubinsky; Cheryl P Kordik; Pauline J Sanfilippo; Wu-Nan Wu; Allen B Reitz
Journal:  Bioorg Med Chem Lett       Date:  2002-09-02       Impact factor: 2.823

6.  In vitro metabolism of the new anxiolytic agent, RWJ-52763 in human hepatic S9 fraction-API-MS/MS identification of metabolites.

Authors:  Wu-Nan Wu; Linda A McKown; Allen B Reitz
Journal:  J Pharm Biomed Anal       Date:  2003-02-05       Impact factor: 3.935

7.  In-vitro metabolism of the new anxiolytic agent, RWJ-50172, in rat hepatic S9 fraction and microbial transformation in fungi, Cunninghamella sp.

Authors:  Wu-Nan Wu; Linda A McKown; John L Melton; Allen B Reitz
Journal:  J Pharm Pharmacol       Date:  2003-08       Impact factor: 3.765
  7 in total
  1 in total

1.  Metabolism of the new anxiolytic agent, a pyrido[1,2-]benzimidazole (PBI) analog (RWJ-53050), in rat and human hepatic S9 fractions, and in dog; identification of cytochrome p450 isoforms mediated in the human microsomal metabolism.

Authors:  Wu-Nan Wu; Linda A McKown; Allen B Reitz
Journal:  Eur J Drug Metab Pharmacokinet       Date:  2006 Oct-Dec       Impact factor: 2.441
  1 in total

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