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Titolo:
CYP2D6 genotype and antipsychotic-induced extrapyramidal side effects in schizophrenic patients
Autore:
Scordo, MG; Spina, E; Romeo, P; Dahl, ML; Bertilsson, L; Johansson, I; Sjoqvist, F;
Indirizzi:
Huddinge Univ Hosp, Karolinska Inst, Dept Med Lab Sci & Technol, Div Clin Pharmacol, S-14186 Huddinge, Sweden Huddinge Univ Hosp Huddinge Sweden S-14186 col, S-14186 Huddinge, Sweden Univ Messina, Policlin Univ, Inst Pharmacol, I-98125 Messina, Italy Univ Messina Messina Italy I-98125 nst Pharmacol, I-98125 Messina, Italy Ctr Mental Hlth, Messina, Italy Ctr Mental Hlth Messina ItalyCtr Mental Hlth, Messina, Italy Univ Messina, Inst Psychiat, Messina, Italy Univ Messina Messina ItalyUniv Messina, Inst Psychiat, Messina, Italy Karolinska Inst, Inst Environm Med, Div Mol Toxicol, S-10401 Stockholm, Sweden Karolinska Inst Stockholm Sweden S-10401 icol, S-10401 Stockholm, Sweden
Titolo Testata:
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 9-10, volume: 56, anno: 2000,
pagine: 679 - 683
SICI:
0031-6970(200012)56:9-10<679:CGAAES>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED MOVEMENT-DISORDERS; POLYMORPHIC HYDROXYLATION; DEBRISOQUINE OXIDATION; PLASMA-LEVELS; GENETIC-POLYMORPHISM; TARDIVE-DYSKINESIA; SWEDISH POPULATION; POOR METABOLIZERS; PHENOTYPE; DISPOSITION;
Keywords:
CYP2D6; genotype; antipsychotic drugs; extrapyramidal side effects;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Scordo, MG Huddinge Univ Hosp, Karolinska Inst, Dept Med Lab Sci & Technol, Div Clin Pharmacol, S-14186 Huddinge, Sweden Huddinge Univ Hosp Huddinge Sweden S-14186 6 Huddinge, Sweden
Citazione:
M.G. Scordo et al., "CYP2D6 genotype and antipsychotic-induced extrapyramidal side effects in schizophrenic patients", EUR J CL PH, 56(9-10), 2000, pp. 679-683

Abstract

Objective: In order to evaluate whether poor metabolizers (PM) of debrisoquine are overrepresented among patients with acute dystonic reactions and chronic movement disorders associated with the administration of antipsychotic drugs, the CYP2D6 genotype was determined in schizophrenic patients. Methods: Allele status for CYP2D6*3, CYP2D6*4, CYP2D6*5, and CYP2D6*6 as well as gene duplication was determined by allele-specific PCR, long-PCR andrestriction fragment length polymorphism analysis (RFLP) in 119 schizophrenic patients (99 males and 20 females). All subjects were treated with antipsychotics metabolized, at least partially, by this isozyme. Sixty-three ofthe patients (52.9%) had a history of extrapyramidal side effects (EPS), while 56 (47.1%) had not experienced such problems (controls). Results: Sixty-five patients (54.6%) were homozygous for a functional CYP2D6*1 allele, 44 (37.0%) were heterozygous for detrimental alleles, and 4 (3.4%), who carried two detrimental alleles, were classified as PM. In six patients (5.0%) duplication of a functional CYP2D6 gene was found, and they were consequently classified as ultrarapid metabolizers (UM). Homo- and heterozygous extensive metabolizers (EM) as well as UM were equally distributedbetween patients with and without EPS, whereas all the PM had a history ofEPS. No significant differences in allele frequencies between the two groups were found. Conclusion: Although the results cannot be considered conclusive due to the small number of PM patients in our study, the PM genotype may be a predisposing factor for antipsychotic-induced EPS. Knowledge of the CYP2D6 genotype, before starting antipsychotic therapy, might be useful in identifying subjects at risk of developing EPS.

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Documento generato il 20/01/20 alle ore 11:17:56