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Cytochrome P450 2D6: Genetic polymorphism in subjects abusing cocaine
Bibliografi
Author:
Chaudhari, Savita D.
;
Sellers, E.
(Advisor)
Topik:
BIOLOGY
;
GENETICS|HEALTH SCIENCES
;
PUBLIC HEALTH
Bahasa:
(EN )
ISBN:
0-612-34079-1
Penerbit:
UNIVERSITY OF TORONTO
Tahun Terbit:
1998
Jenis:
Theses - Dissertation
Fulltext:
MQ34079.pdf
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)
Abstract
The debrisoquine-4-hydroxylase polymorphism is a genetic variation in oxidative drug metabolism characterized by two phenotypes, extensive metabolizers (EM) and the poor metabolizers (PM). Five to 10% of the Caucasian populations of Europe and North America are of the PM phenotype and are unable to metabolize debrisoquine, dextromethorphan and numerous other drugs. The impaired drug metabolism in PMs is due to the absence of the cytochrome P450 2D6 (CYP2D6) protein. The dextromethorphan metabolizer phenotype in 59 current and former (within the past two years) regular cocaine users (meeting DSM-IV criteria for psychoactive substance abuse or dependence for cocaine) was determined after oral administration of a 30 mg dose. In eight hours-post dose urine samples the log O-demethylation ratio was determined by HPLC and all 59 subjects were identified as EMs. Genotyping results by PCR were consistent with the EM phenotype for all 59 subjects. Hair samples taken from the subjects were analysed for a metabolite of cocaine to confirm self-reported drug use history. The phenotyping results of the cocaine dependent population were compared to a non-cocaine dependent control population (n = 210). The EM frequency in the control group was found to be 93% and the PM frequency was 7%. Using Chi square analysis, a significant difference was found between the EM and PM genotypes of the cocaine dependent population and the control groups (p $<$ 0.05). The homogeneity of the EM phenotype among a sample of cocaine users, and the complete absence of PMs, suggests that individuals with the PM phenotype may be protected against the risk of development of cocaine use/dependence.
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