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Titolo:
Polymorphic cytochromes P450 and drugs used in psychiatry
Autore:
Coutts, RT; Urichuk, LJ;
Indirizzi:
Univdalberta, Dept Psychiat, Neurochem Res Unit, Edmonton, AB T6G 2B7, Cana Univ Alberta Edmonton AB Canada T6G 2B7 Unit, Edmonton, AB T6G 2B7, Cana
Titolo Testata:
CELLULAR AND MOLECULAR NEUROBIOLOGY
fascicolo: 3, volume: 19, anno: 1999,
pagine: 325 - 354
SICI:
0272-4340(199906)19:3<325:PCPADU>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-LIVER-MICROSOMES; MEPHENYTOIN OXIDATION POLYMORPHISMS; SEROTONIN REUPTAKE INHIBITORS; DEBRISOQUINE HYDROXYLATION POLYMORPHISM; POOR METABOLIZER PHENOTYPE; CYP2D6 GENE POLYMORPHISM; S-MEPHENYTOIN; PARKINSONS-DISEASE; IN-VITRO; CLINICAL PHARMACOKINETICS;
Keywords:
drug metabolism; cytochromes P450; monooxygenases; polymorphism; CYP2D6; CYP2C19; CYP2C9; amino acid sequences; defective genes; phenotyping; genotyping; ethnic differences in drug metabolism; CYP enzyme inhibitors; CYP enzyme substrates; drug/drug interactions; poor metabolizers; extensive metabolizers; ultrarapid metabolizers; diet; age; cancer; Parkinson's disease; schizophrenia; Alzheimer's disease; epilepsy;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
178
Recensione:
Indirizzi per estratti:
Indirizzo: Coutts, RT Univdalberta, Dept Psychiat, Neurochem Res Unit, Edmonton, AB T6G 2B7, Cana Univ Alberta Edmonton AB Canada T6G 2B7 nton, AB T6G 2B7, Cana
Citazione:
R.T. Coutts e L.J. Urichuk, "Polymorphic cytochromes P450 and drugs used in psychiatry", CELL MOL N, 19(3), 1999, pp. 325-354

Abstract

1. The cytochrome P450 monooxygenases, CYP2D6, CYP2C19, and CYP2C9, display polymorphism. CYP2D6 and CYP2C19 have been studied extensively, and despite their low abundance in the liver, they catalyze the metabolism of many drugs.2. CYP2D6 has numerous allelic variants, whereas CYP2C19 has only two. Most variants are translated into inactive, truncated protein or fail to express protein.3. CYP2C9 is expressed as the wild-type enzyme and has two variants, in each of which one amino acid residue has been replaced.4. The nucleotide base sequences of the cDNAs of the three polymorphic genes and their variants have been determined, and the proteins derived from these genes have been characterized.5. An absence of CYP2D6 and/or CYP2C19 in an individual produces a poor metabolizer (PM) of drugs that are substrates of these enzymes.6. When two drugs that are substrates for a polymorphic CIP enzyme are administered concomitantly, each will compete for that enzyme and competitively inhibit the metabolism of the other substrate. This can result in toxicity.7. Patients can be readily phenotyped or genotyped to determine their CYP2D6 or CYP2C19 enzymatic status. Poor metabolizers (PMs), extensive metabolizers (EMs), and ultrarapid metabolizers (URMs) can be identified.8. Numerous substrates and inhibitors of CYP2D6, CYP2C19, and CYP2C9 are identified. 9. An individual's diet and age can influence CYP enzyme activity.10. CYP2D6 polymorphism has been associated with the risk of onset of various illnesses, including cancer, schizophrenia, Parkinson's disease, Alzheimer's disease, and epilepsy.

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Documento generato il 19/01/20 alle ore 12:09:02