Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function. (Q34273354)

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31 January 2020

title

Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function (English)

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31 January 2020

1

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31 January 2020

Roberto Viviani

series ordinal

3

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31 January 2020

author name string

J Brockmöller

series ordinal

2

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31 January 2020

language of work or name

English

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publication date

8 May 2012

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31 January 2020

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https://www.ebi.ac.uk/europepmc/webservices/rest/search?query=EXT_ID:22565785%20AND%20SRC:MED&resulttype=core&format=json

31 January 2020

volume

18

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31 January 2020

issue

3

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31 January 2020

page(s)

273-287

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https://scigraph.springernature.com/pub.10.1038/mp.2012.42

31 January 2020

exact match

0 references

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21 January 2018

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21 January 2018

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21 January 2018

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21 January 2018

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A default mode of brain function

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Amplitude-modulated continuous arterial spin-labeling 3.0-T perfusion MR imaging with a single coil: feasibility study

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21 January 2018

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Potentials and challenges for arterial spin labeling in pharmacological magnetic resonance imaging

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Baseline brain perfusion and the serotonin transporter promoter polymorphism.

21 January 2018

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Feelings of fatigue and psychopathology: a conceptual history

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Association between cytochrome P450 2D6 genotype and harm avoidance

21 January 2018

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Relation between CYP2D6 phenotype and genotype and personality in healthy volunteers

21 January 2018

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No association between CYP2D6 polymorphisms and personality trait in Japanese

21 January 2018

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Cytochrome P450 2D6 polymorphism and character traits

21 January 2018

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Relationship between Type A and B personality and debrisoquine hydroxylation capacity

21 January 2018

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Interethnic variation of drug metabolism

21 January 2018

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Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales

21 January 2018

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CYP2C19 polymorphism affects personality traits of Japanese females.

21 January 2018

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Association between cytochrome P450 (CYP) 2C19 polymorphisms and harm avoidance in Japanese.

21 January 2018

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Lack of association between schizophrenia and polymorphisms in dopamine metabolism and transport genes

21 January 2018

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https://api.crossref.org/works/10.1038%2FMP.2012.42

No association between schizophrenia and polymorphisms within the genes for debrisoquine 4-hydroxylase (CYP2D6) and the dopamine transporter (DAT).

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Molecular diversity at the CYP2D6 locus in healthy and schizophrenic southern Brazilians

21 January 2018

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Polymorphic debrisoquine oxidation and acute neuroleptic-induced adverse effects

21 January 2018

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Debrisoquine 4-hydroxylase (CYP2D) locus and possible susceptibility to schizophrenia

21 January 2018

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The impact of the CYP2D6 polymorphism on haloperidol pharmacokinetics and on the outcome of haloperidol treatment.

21 January 2018

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Xenobiotic metabolizing and transporter genes: gene-gene interactions in schizophrenia and related disorders.

21 January 2018

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Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19.

21 January 2018

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Fatal intoxication cases: cytochrome P450 2D6 and 2C19 genotype distributions

21 January 2018

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High frequency of occurrence of CYP2D6 gene duplication/multiduplication indicating ultrarapid metabolism among suicide cases

21 January 2018

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CYP2D6 genotypes and depressive symptoms during late pregnancy and postpartum.

21 January 2018

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Generation of mice transgenic for human CYP2C18 and CYP2C19: characterization of the sexually dimorphic gene and enzyme expression

21 January 2018

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https://api.crossref.org/works/10.1038%2FMP.2012.42

CYP2C9 gene and susceptibility to major depressive disorder.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Association between the CYP2D6*4 polymorphism and depression or anxiety in the elderly

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Antidepressant medication prevents suicide in depression

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Identification and characterization of CYP3A4*20, a novel rare CYP3A4 allele without functional activity

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Genetic variability in CYP2A6 and the pharmacokinetics of nicotine

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Glucuronidation enzymes, genes and psychiatry

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Pharmacogenetics of antidepressant medication intolerance

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Amitriptyline or not, that is the question: pharmacogenetic testing of CYP2D6 and CYP2C19 identifies patients with low or high risk for side effects in amitriptyline therapy

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Evaluation of the influence of sex and CYP2C19 and CYP2D6 polymorphisms in the disposition of citalopram.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Heterozygous mutation in CYP2C19 significantly increases the concentration/dose ratio of racemic citalopram and escitalopram (S-citalopram).

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Impact of CYP2C19 phenotypes on escitalopram metabolism and an evaluation of pupillometry as a serotonergic biomarker.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Genetic polymorphisms of cytochrome P450 enzymes influence metabolism of the antidepressant escitalopram and treatment response.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Kinetics of omeprazole and escitalopram in relation to the CYP2C19*17 allele in healthy subjects

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

No evidence of increased adverse drug reactions in cytochrome P450 CYP2D6 poor metabolizers treated with fluoxetine or nortriptyline

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Influence of CYP2C9, 2C19 and 2D6 genetic polymorphisms on the steady-state plasma concentrations of the enantiomers of fluoxetine and norfluoxetine

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Relationship between clinical effects of fluvoxamine and the steady-state plasma concentrations of fluvoxamine and its major metabolite fluvoxamino acid in Japanese depressed patients

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Polymorphisms in the 5-hydroxytryptamine 2A receptor and CytochromeP4502D6 genes synergistically predict fluvoxamine-induced side effects in japanese depressed patients

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Dose-dependent effect of the CYP2D6 genotype on the steady-state fluvoxamine concentration

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Links among paroxetine-induced sexual dysfunctions, gender, and CYP2D6 activity.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Severe adverse effects in a newborn with two defective CYP2D6 alleles after exposure to paroxetine during late pregnancy

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Life-threatening serotonin syndrome in a patient with chronic heart failure and CYP2D6*1/*5.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Population pharmacokinetic analysis of mirtazapine

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Duloxetine pharmacokinetics are similar in Japanese and Caucasian subjects

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Pharmacokinetics and tolerability of duloxetine following oral administration to healthy Chinese subjects.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Maprotiline metabolism appears to co-segregate with the genetically-determined CYP2D6 polymorphic hydroxylation of debrisoquine

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Steady-state concentrations of mirtazapine, N-desmethylmirtazapine, 8-hydroxymirtazapine and their enantiomers in relation to cytochrome P450 2D6 genotype, age and smoking behaviour.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Cytochrome P450 2D6 phenotype predicts antidepressant efficacy of venlafaxine: a secondary analysis of 4 studies in major depressive disorder

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Venlafaxine metabolism as a marker of cytochrome P450 enzyme 2D6 metabolizer status.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Differential outcomes from metabolic ratios in the identification of CYP2D6 phenotypes--focus on venlafaxine and O-desmethylvenlafaxine

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Effect of Cytochrome P450 Enzyme Polymorphisms on Pharmacokinetics of Venlafaxine

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Failure to respond to treatment with typical antipsychotics is not associated with CYP2D6 ultrarapid hydroxylation.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on long-term antipsychotic treatment

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Maintenance therapy with zuclopenthixol decanoate: associations between plasma concentrations, neurological side effects and CYP2D6 genotype

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

CYP2D6 polymorphisms and atypical antipsychotic weight gain.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Carriers of the UGT1A4 142T>G gene variant are predisposed to reduced olanzapine exposure--an impact similar to male gender or smoking in schizophrenic patients

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Impact of CYP2D6 genotype on steady-state serum concentrations of risperidone and 9-hydroxyrisperidone in patients using long-acting injectable risperidone

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naïve patients with first-episode schizophrenia treated with risperidone

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

A population pharmacokinetic evaluation of the influence of CYP2D6 genotype on risperidone metabolism in patients with acute episode of schizophrenia

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Pharmacokinetics and pharmacodynamics of etizolam are influenced by polymorphic CYP2C19 activity

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Effect of the UGT2B15 genotype on the pharmacokinetics, pharmacodynamics, and drug interactions of intravenous lorazepam in healthy volunteers

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Evidence for oxazepam as an in vivo probe of UGT2B15: oxazepam clearance is reduced by UGT2B15 D85Y polymorphism but unaffected by UGT2B17 deletion

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Contribution of individual cytochrome P450 isozymes to the O-demethylation of the psychotropic beta-carboline alkaloids harmaline and harmine.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

5-Hydroxytryptamine is biotransformed by CYP2C9, 2C19 and 2B6 to hydroxylamine, which is converted into nitric oxide

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Metabolism of melatonin by human cytochromes p450.

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: I. Identification of polymorphisms in the 5'-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Characterization of human hepatic and extrahepatic UDP-glucuronosyltransferase enzymes involved in the metabolism of classic cannabinoids

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Effect of two mutations of human CYP1B1, G61E and R469W, on stability and endogenous steroid substrate metabolism

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Involvement of CYP2J2 and CYP4F12 in the metabolism of ebastine in human intestinal microsomes

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

A Population-Average, Landmark- and Surface-based (PALS) atlas of human cerebral cortex

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Cytochrome P -450 activities in human and rat brain microsomes

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Relationship between personality and debrisoquine hydroxylation capacity

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Lack of association between schizophrenia and theCYPZD6 gene polymorphisms

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Low frequency of CYP2D6 poor metabolizers among schizophrenia patients

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Non-functional CYP2D6 alleles and risk for neuroleptic-induced movement disorders in schizophrenic patients

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Pharmacokinetics of venlafaxine extended release 75 mg and desvenlafaxine 50 mg in healthy CYP2D6 extensive and poor metabolizers: a randomized, open-label, two-period, parallel-group, crossover study

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

Cytochrome P450 2D6 (CYP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions

21 January 2018

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Pharmacogenetics-based therapeutic recommendations — ready for clinical practice?

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Serum prolactin levels, plasma risperidone levels, polymorphism of cytochrome P450 2D6 and clinical response in patients with schizophrenia

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

The cytochrome P450 2D6 (CYP2D6) enzyme polymorphism: screening costs and influence on clinical outcomes in psychiatry

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Increased incidence of CYP2D6 gene duplication in patients with persistent mood disorders: ultrarapid metabolism of antidepressants as a cause of nonresponse. A pilot study

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

What is clinical utility and why should we care?

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Regiospecific expression of cytochrome P-450s and microsomal epoxide hydrolase in human brain tissue

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

The clinical impact of ABCB1 polymorphisms on the treatment of psychiatric diseases

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Human CYP2D6 and mouse CYP2Ds: organ distribution in a humanized mouse model

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Genetic variation in CYP2D6 impacts neural activation during cognitive tasks in humans.

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Debrisoquine hydroxylation polymorphism and personality

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Association of CYP2D6 Genotypes and Personality Traits in Healthy Individuals

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Antipsychotic drug-induced movement disorders in schizophrenics in relation to CYP2D6 genotype

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

An association study of debrisoquine hydroxylase (CYP2D6) polymorphisms in schizophrenia

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Lack of association between debrisoquine 4-hydroxylase (CYP2D6) gene polymorphisms and schizophrenia.

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

CYP2D6 in the Brain: Impact on Suicidality

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

CYP2D6 and the severity of suicide attempts.

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

CYP2D6 polymorphism in patients with eating disorders

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Association between CYP2C19*17 and metabolism of amitriptyline, citalopram and clomipramine in Dutch hospitalized patients

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

The CYP2C19*17 genotype is associated with lower imipramine plasma concentrations in a large group of depressed patients

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Pharmacokinetics of Mirtazapine: Enantioselective Effects of the CYP2D6 Ultra Rapid Metabolizer Genotype and Correlation with Adverse Effects

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Polymorphic drug metabolism in schizophrenic patients with tardive dyskinesia

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Association between cytochrome P4502D6 (CYP2D6) genotype, antipsychotic exposure, and abnormal involuntary movement scale (AIMS) score

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

CYP2D6 genotype and antipsychotic-induced extrapyramidal side effects in schizophrenic patients

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

CYP2D6 Genotyping in Patients on Psychoactive Drug Therapy

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Depot haloperidol treatment in outpatients with schizophrenia on monotherapy: impact of CYP2D6 polymorphism on pharmacokinetics and treatment outcome

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Factors Affecting Drug Concentrations and QT Interval During Thioridazine Therapy

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Impact of the CYP2D6 genotype on steady-state serum concentrations of aripiprazole and dehydroaripiprazole

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Clozapine-induced agranulocytosis and hereditary polymorphisms of clozapine metabolizing enzymes: no association with myeloperoxidase and cytochrome P4502D6

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Epidemiology and characteristics of adverse drug reactions caused by drug-drug interactions.

1 reference

https://api.crossref.org/works/10.1038%2FMP.2012.42

7 January 2021

Identifiers

DOI

10.1038/MP.2012.42

1 reference

https://www.ebi.ac.uk/europepmc/webservices/rest/search?query=EXT_ID:22565785%20AND%20SRC:MED&resulttype=core&format=json

31 January 2020

1 reference