Document Detail


Pharmacogenetics of naltrexone in asian americans: a randomized placebo-controlled laboratory study.
MedLine Citation:
PMID:  21900886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent clinical and laboratory studies have shown that the effects of naltrexone for alcoholism may be moderated by the Asn40Asp single-nucleotide polymorphism (SNP) of the μ-opioid receptor gene (OPRM1). Allele frequencies for this polymorphism, however, have been shown to vary substantially as a function of ethnic background, such that individuals of Asian descent are more likely to carry the minor (Asp40) allele. The objective of this study is to test the naltrexone pharmacogenetic effects of the Asn40Asp SNP in a sample of Asian Americans. This study consists of a double-blinded, randomized, placebo-controlled laboratory trial of naltrexone. Participants (n=35, 10 females; 13 Asn40Asn and 22 Asp40 carriers) were non-treatment-seeking heavy drinkers recruited from the community. After taking naltrexone or placebo, participants completed an intravenous alcohol administration session. The primary outcome measures were subjective intoxication and alcohol craving. Results suggested that Asp40 carriers experienced greater alcohol-induced sedation, subjective intoxication, and lower alcohol craving on naltrexone, as compared to placebo, and to Asn40 homozygotes. There results were maintained when controlling for ALDH2 (rs671) and ADH1B (rs1229984) markers and when examining the three levels of OPRM1 genotype, thereby supporting an OPRM1 gene dose response. These findings provide a much-needed extension of previous studies of naltrexone pharmacogenetics to individuals of Asian descent, an ethnic group more likely to express the minor allele putatively associated with improved biobehavioral and clinical response to this medication. These findings help further delineate the biobehavioral mechanisms of naltrexone and its pharmacogenetics.
Authors:
Lara A Ray; Spencer Bujarski; Pauline F Chin; Karen Miotto
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-07
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  37     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-14     Completed Date:  2012-04-17     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  445-55     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adrenocorticotropic Hormone / blood
Adult
Alcohol Dehydrogenase / genetics
Alcoholic Intoxication / prevention & control*
Alcoholism / drug therapy,  genetics*
Aldehyde Dehydrogenase / genetics
Alleles
Asian Americans / genetics*
Behavior, Addictive / drug therapy*
Double-Blind Method
Ethanol / adverse effects*,  antagonists & inhibitors
Female
Genotype
Humans
Hydrocortisone / blood
Male
Naltrexone / therapeutic use*
Narcotic Antagonists / therapeutic use
Polymorphism, Single Nucleotide
Receptors, Opioid, mu / genetics*
Grant Support
ID/Acronym/Agency:
L30 AA017082/AA/NIAAA NIH HHS; M01-RR00865/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Narcotic Antagonists; 0/Receptors, Opioid, mu; 3K9958V90M/Ethanol; 5S6W795CQM/Naltrexone; 9002-60-2/Adrenocorticotropic Hormone; EC 1.1.1.1/ADH1B protein, human; EC 1.1.1.1/Alcohol Dehydrogenase; EC 1.2.1.3/ALDH2 protein, human; EC 1.2.1.3/Aldehyde Dehydrogenase; WI4X0X7BPJ/Hydrocortisone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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