Drug metabolism for the perplexed medicinal chemist.

Détails

ID Serval
serval:BIB_A552215F9E2F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Drug metabolism for the perplexed medicinal chemist.
Périodique
Chemistry & Biodiversity
Auteur(s)
Testa Bernard
ISSN
1612-1880[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
6
Numéro
11
Pages
2055-2070
Langue
anglais
Résumé
Two related and significant issues may elicit perplexity in medicinal chemists and are discussed here. First, a broad presentation of the pharmacological and toxicological consequences of drug metabolism should justify the significance of drug metabolism and serve as an incentive to further study. When comparing the pharmacological activities of a drug and its metabolite(s), a continuum is found which ranges from soft drugs (no active metabolites) to prodrugs (inactive per se, as illustrated here with clopidogrel and prasugrel). Innumerable intermediate cases document drugs whose activity is shared by one or more metabolites, as exemplified with tamoxifen. The toxicological consequences of metabolism at the molecular, macromolecular, and macroscopic levels are manyfold. A brief overview is offered together with a summary of the reactions of toxification and detoxification of the antiepileptic valproic acid. The second issue discussed in the review is a comparison of the relative significance of cytochromes P450 and other oxidoreductases (EC 1), hydrolases (EC 3), and transferases (EC 2) in drug metabolism, based on a 'guesstimate' of the number of drug metabolites that are known to be produced by them. The conclusion is that oxidoreductases are the main enzymes responsible for the formation of toxic or active metabolites, whereas transferases play the major role in producing inactive and nontoxic metabolites.
Mots-clé
Valproic Acid, Active Metabolite, In-Vitro, (E)-2-Propyl-2,4-Pentadienoic Acid, Toxic Metabolite, Breast-Cancer, Biochemistry, Discovery, Clopidogrel, Prasugrel
Pubmed
Web of science
Création de la notice
21/12/2009 16:55
Dernière modification de la notice
03/03/2018 20:15
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