Smoking risk and the likelihood of quitting among African-American female light and heavy smokers.

While African-American females are more likely to be light smokers compared to their counterparts of other racially classified social groups (RCSGs), they are more likely to carry a heavier burden of smoking-related morbidity and mortality. Thus, it is critical that African-American female light smokers are targeted to engage in smoking cessation. Research has revealed that African-American women are less likely to have a successful quit attempt following a cessation intervention than females from other RCSGs.

Nicotine increases dopamine clearance in medial prefrontal cortex in rats raised in an enriched environment.

Environmental enrichment results in differential behavioral and neurochemical responsiveness to nicotine. The present study investigates dopamine clearance (CL(DA) ) in striatum and medial prefrontal cortex (mPFC) using in vivo voltammetry in rats raised in enriched (EC) or impoverished conditions (IC) and administered nicotine (0.4 mg/kg) or saline.

A study of genetic (CYP2D6 and ABCB1) and environmental (drug inhibitors and inducers) variables that may influence plasma risperidone levels.

Risperidone (R) is metabolized to 9-hydroxyrisperidone (9-OHR) by cytochrome P450 2D6 (CYP2D6). The main objective of this naturalistic study was to investigate the variables associated with two plasma ratios: the plasma R:9-OHR concentration ratio and the total concentration-to-dose (C:D) ratio. These ratios were studied as continuous measures by linear regression analyses and as three dichotomous variables in logistic regression analyses: R:9-OHR ratio >1 (indicative of lack of CYP2D6 activity), C:D ratio >14 (indicative of diminished R elimination), and C:D ratio <3.

Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation.

Nornicotine, a tobacco alkaloid and N-demethylated nicotine metabolite, releases DA from superfused rat striatal slices in a mecamylamine-sensitive manner, indicating nicotinic receptor (nAChR) modulation of this response. The current study determined the effect of nornicotine on rat striatal dopamine transporter (DAT) function using in vivo voltammetry. In a dose-related and mecamylamine-sensitive manner, nornicotine (0.

New cytochrome P450 2D6*56 allele identified by genotype/phenotype analysis of cryopreserved human hepatocytes.

Genotype/phenotype analysis with human hepatocytes has identified a new inactive CYP2D6 allele, CYP2D6*56. Cryopreserved human hepatocytes from 51 livers were evaluated for CYP2D6 activity with dextromethorphan as the probe substrate. Hepatocyte lots that lacked CYP2D6 activity were further evaluated for CYP2D6 expression and known genetic variations, including CYP2D6*2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *14, *15, *17, *18, *19, *20, *25, *26, *29, *30, *35, *40, *41, *43, and various multiple copy CYP2D6 alleles (*1xn, *2xn, and *4xn) by the AmpliChip CYP450 prototype microarray (Roche Molecular Systems, Inc.

CYP2D6 genetic variation in healthy adults and psychiatric African-American subjects: implications for clinical practice and genetic testing.

Limited information is available on the frequency of the many CYP2D6 alleles found in African-Americans. DNA was isolated and genetic testing was performed on samples from 222 African-Americans, healthy controls (n=131), and psychiatric patients (n=91). Each DNA was tested for CYP2D6 alleles *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *14, *15, *17, *18, *19, *20, *25, *26, *29, *30, *31, *35, *36, *37, *40, *41 and *43 and 8 multiple copy alleles (*1xn, *2xn, *4xn, *41xn, *2Lxn, *17xn, *35xn and *10xn) using the AmpliChip CYP450 prototype microarray assay, along with allele-specific-PCR and PCR restriction fragment length polymorphism methods.

Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness.

This study tested the association between tardive dyskinesia (TD) and polymorphic variations in (a) 2 cytochrome P450 (CYP) genes (CYP2D6 or CYP3A5), (b) 2 DRD2 variants (Ser311Cys and -141C Ins/del) and the Ser9Gly DRD3 variants, (c) 2 glutathione S-transferases (GSTT1 and GSTM1), and (d) variations in the PgP gene, MDR1. The study sample included 516 severely mentally ill patients from Central Kentucky facilities. Logistic regression models that included clinical variables associated with TD were developed.

Nipecotic acid: systemic availability and brain delivery after nasal administration of nipecotic acid and n-butyl nipecotate to rats.

Purpose: The purpose of this research was to characterize nipecotic acid pharmacokinetics in blood and brain after intravenous (i.v.) and nasal administration of nipecotic acid and its n-butyl ester.

The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation.

Objective: The cytochrome P450 2D6 (CYP2D6) enzyme metabolizes risperidone. CYP2D6 poor metabolizers have no CYP2D6 activity (7% of whites and 1%-2% of other races). This study tested whether the CYP2D6 poor metabolizer phenotype was associated with adverse drug reactions (ADRs) and discontinuation due to ADRs.

Haloperidol half-life after chronic dosing.

In normal subjects after a single oral dose, haloperidol half-life has been reported to range 14.5-36.7 hours (or up to 1.

Assay for nipecotic acid in small blood samples by gas chromatography-mass spectroscopy.

An analytical method for nipecotic acid quantification in rat blood was developed utilizing a stable isotope internal standard and capillary gas chromatography-mass spectroscopy. The method involves a solid phase extraction step followed by a two-step derivatization. The analytes are separated by capillary gas chromatography and detected by selected ion monitoring of their base peaks at 180 and 185 m/z, respectively.

CYP2D6, GST-M1 and GST-T1 enzymes: expression in parathyroid gland and association with the parathyroid hormone concentration during early renal replacement therapy.

Aims: The purpose of this research was to characterize CYP2D6, GST-M1 and GST-T1 enzyme expression in human parathyroid tissue, and to determine whether or not there is any association between deficiencies in these enzymes and serum parathyroid hormone concentrations in patients with end-stage renal disease.

Methods: Surgical human parathyroid tissue was obtained and evaluated by immunohistochemistry for cellular localization of CYP2D6, GST-M1 and GST-T1 and colocalization of CYP2D6 with parathyroid hormone. Blood samples were collected from 328 Caucasian patients with end-stage renal disease for genetic testing of CYP2D6*3, *4, *5, *6, *7 and GST-M1*0 and GST-T1*0 alleles.

Comparison of two CYP2D6 genotyping methods and assessment of genotype-phenotype relationships.

Background: There have been no published reports comparing the CYP450 GeneChip microarray assay with more standard methods of genetic testing.

Methods: We collected 20-mL blood samples from 236 volunteers for DNA isolation and testing before each individual ingested 60 mg of dextromethorphan, and collected their urine. CYP2D6 alleles *3 to *7, *9, *17, and *41, and multiple CYP2D6 gene copies were tested by allele-specific PCR (AS-PCR), whereas alleles *2 to *4 and *6 to *11 were tested by the Affymetrix CYP450 GeneChip assay.

Racial differences in parathyroid hormone levels in patients with secondary hyperparathyroidism.

Aim: African-Americans (AA) with normal renal function have higher parathyroid hormone (PTH) levels than Caucasians (C). This difference was also noted in cross-sectional studies of patients on dialysis. In this study, we evaluated patients with end-stage renal disease who have just began dialysis and who were not receiving any vitamin D therapy.

[Distinguishing CYP2D6 homozygous and heterozygous extensive metabolizers by dextromethorphan phenotyping].

A more sensitive procedure was developed to phenotype cytochrome P450 2D6 metabolism by a less toxic probe drug--dextromethorphan. The sensitivity of the determination of dextromethorphan in urine samples was up to 1 ng.ml-1.

The CYP2C19 enzyme polymorphism.

The genetic test is gradually replacing probe drugs as the primary tool for screening populations for the CYP2C19 polymorphism. A full appreciation for the clinical and toxicological relevance of this genetic variation is presently limited. Further research is needed in several areas.

Correlation between cytochrome P-450 CYP2D6 (CYP2D6) genotype and phenotype.

Aim: To study the correlation between CYP2D6 genotype and its phenotype.

Methods: CYP2D6 genotyping was made by detecting CYP2D6*3, *4, *6, and *7 alleles with an allele-specific polymerase chain reaction procedure.

Results: The CYP2D6 genotypes were well correlated with its phenotypes in all 125 extensive metabolizers and in 43 poor metabolizers.

Extension of a pilot study: impact from the cytochrome P450 2D6 polymorphism on outcome and costs associated with severe mental illness.

The influence of cytochrome P450 2D6 (CYP2D6) genetic variability was examined in psychiatric inpatients by evaluating adverse drug events (ADEs), hospital stays, and total costs over a 1-year period in an extension of a previously published brief report. One hundred consecutive psychiatric patients from Eastern State Hospital in Lexington, Kentucky, were genotyped for CYP2D6 expression. ADEs were evaluated by a neurologic rating scale, modified Udvalg for Kliniske Undersogelser Side Effect Rating Scale, or chart review.

A pilot study on risperidone metabolism: the role of cytochromes P450 2D6 and 3A.

Background: The limited available information on plasma risperidone levels shows a stable relationship between daily doses of risperidone and total plasma concentration (risperidone plus its active metabolite 9-hydroxyrisperidone). The ratio between risperidone and 9-hydroxyrisperidone characterizes cytochrome P450 2D6 (CYP2D6) status. According to the manufacturer, the CYP2D6 genotype or drugs that influence CYP2D6 or other cytochrome P450 isoenzyme activity are not expected to be clinically significant.

Pilot study of the cytochrome P450-2D6 genotype in a psychiatric state hospital.

Objective: The authors conducted a pilot study to develop preliminary data on the frequency of cytochrome P450-2D6 (CYP2D6) genotypes in state psychiatric hospital patients and to establish population sizes needed to determine potential clinical relevance in therapeutic outcome.

Method: One hundred consecutive inpatients at Eastern State Hospital in Kentucky who provided informed consent were genotyped at the CYP2D6 locus during their hospital stay.

Results: Twelve of the patients were CYP2D6 deficient, and four carried the *1Xn or *2Xn allele associated with ultrarapid metabolism; all of these patients were Caucasian (N=87).