Titre du document / Document title
Differential metabolism of alprazolam by liver and brain cytochrome (P4503A) to pharmacologically active metabolite
Auteur(s) / Author(s)
PAI H. V.
(1 2) ;
UPADHYA S. C.
(1 2) ;
CHINTA S. J.
(1) ;
HEGDE S. N.
(1) ;
RAVINDRANATH V.
(1 2) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Bangalore, INDE
(2) National Brain Research Centre, ICGEB Campus, Aruna Asaf Ali Marg, New Delhi, INDE
Résumé / Abstract
Cytochrome P450 (P450) is a superfamily of enzymes which mediates metabolism of xenobiotics including drugs. Alprazolam, an anti-anxiety agent, is metabolized in rat and human liver by P4503A1 and P4503A4 respectively, to 4-hydroxy alprazolam (4-OHALP, pharmacologically less active) and α-hydroxy alprazolam (a-OHALP, pharmacologically more active). We examined P450 mediated metabolism of alprazolam by rat and human brain microsomes and observed that the relative amount of α-OHALP formed in brain was higher than liver. This biotransformation was mediated by a P450 isoform belonging to P4503A subfamily, which is constitutively expressed in neuronal cells in rat and human brain. The formation of larger amounts of α-OHALP in neurons points to local modulation of pharmacological activity in brain, at the site of action of the anti-anxiety drug. Since hydroxy metabolites of alprazolam are hydrophilic and not easily cleared through blood-CSF barrier, α-OHALP would potentially have a longer half-life in brain.
Revue / Journal Title
Pharmacogenomics journal
ISSN 1470-269X
Source / Source
2002, vol. 2, n
o4, pp. 243-258 [16 page(s) (article)] (25 ref.)
Langue / Language
Anglais
Editeur / Publisher
Nature Publishing, Basingstoke, ROYAUME-UNI
(2001)
(Revue)
Mots-clés anglais / English Keywords
Vertebrata ;
Mammalia ;
Rodentia ;
Enzyme ;
Oxidoreductases ;
Benzodiazepine derivatives ;
Messenger RNA ;
Localization ;
Microsome ;
In vitro ;
Isozyme ;
Human ;
Animal ;
Rat ;
Unspecific monooxygenase ;
Brain (vertebrata) ;
Liver ;
Cytochrome P450 ;
Metabolism ;
Comparative study ;
Psychotropic ;
Tranquillizer ;
Alprazolam ;
Mots-clés français / French Keywords
Vertebrata ;
Mammalia ;
Rodentia ;
Enzyme ;
Oxidoreductases ;
Benzodiazépine dérivé ;
RNA messager ;
Localisation ;
Microsome ;
In vitro ;
Isozyme ;
Homme ;
Animal ;
Rat ;
Unspecific monooxygenase ;
Encéphale ;
Foie ;
Cytochrome P450 ;
Métabolisme ;
Etude comparative ;
Psychotrope ;
Tranquillisant ;
Alprazolam ;
Mots-clés espagnols / Spanish Keywords
Vertebrata ;
Mammalia ;
Rodentia ;
Enzima ;
Oxidoreductases ;
Benzodiazepina derivado ;
RNA mensajero ;
Localización ;
Microsoma ;
In vitro ;
Isozima ;
Hombre ;
Animal ;
Rata ;
Unspecific monooxygenase ;
Encéfalo ;
Hígado ;
Citocromo P450 ;
Metabolismo ;
Estudio comparativo ;
Psicotropo ;
Tranquilizante ;
Alprazolam ;
Localisation / Location
INIST-CNRS, Cote INIST : 27122, 35400010829514.0050
Nº notice refdoc (ud4) : 13874283
