Authors: W. N. Wu; L. A. McKown

Source: Current Drug Metabolism, Volume 1, Number 3, November 2000 , pp. 255-270(16)

Publisher: Bentham Science Publishers

Abstract:

Compound biotransformation is a very important research area for drug discovery and development. In this review, publications from the metabolism studies of ten compounds, seven CNS and three cardiovascular agents, from the Johnson & Johnson Corp. were reviewed. The seven CNS compounds are: three antipsychotic agents, mazapertine (arypiperazine analog), RWJ-46344 (arypiperidine analog) and risperidone (aryisoxazole-piperidine analog), one antidepressant, etoperidone (arypiperazine analog), one anxiolytic agent, fenobam (aryimidazole urea analog), one muscle relaxant, xilobam (pyrrolidinylidene urea analog), and one antiepileptic agent, topiramate (fructopyranose sulfamate analog). The three cardiovascular agents are: two arylalkylamine calcium channel blockers, bepridil and RWJ- 26240, and one thioindolaminidine antianginal agent, RWJ-34130. Other antipsychotic and antidepressant agents with similar analogs (ziprasidone, trazodone and nefazodone) as well as other similar analogs of calcium channel blockers (verapamil) are discussed. In this article, excretion and metabolism (in vitro, in vivo) of compounds are reviewed from the CNS agents to the cardiovascular agents, including structures of parent compounds, their metabolites, metabolic pathways, and methods for the isolation, profiling, quantification and structural identification of unchanged compounds and metabolites. Pharmacological activities of parent compounds and their metabolites are also briefly discussed.

Keywords: Biotransformation; RWJ-34130; antipsychotic; thioindolaminidine; verapamil; pyrrolidinylidene; nefazodone

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389200003338965

Affiliations: 1: Division of Preclinical Development, The R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477, USA.

Publication date: 2000-11-01

More about this publication?

• Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:
  
  In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.

Related content

• In this: publication
• By this: publisher
• In this Subject: Anatomy & Physiology ,  Pharmacology
• By this author: W. N. Wu ;  L. A. McKown

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers