当前位置： SCI文献检索 > EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > No major role of norepinephrine transporter gene variations in the cardiostimulant effects of MDMA.

No major role of norepinephrine transporter gene variations in the cardiostimulant effects of MDMA.

Abstract：

PURPOSE:Methylenedioxymethamphetamine (MDMA, ecstasy) is used recreationally and frequently leads to sympathomimetic toxicity. MDMA produces cardiovascular and subjective stimulant effects that were shown to partially depend on the norepinephrine transporter (NET)-mediated release of norepinephrine and stimulation of α1-adrenergic receptors. Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the NET gene (SLC6A2) may explain interindividual differences in the acute stimulant-type responses to MDMA in humans. METHODS:We characterized the effects of common genetic variants of the SLC6A2 gene (rs168924, rs47958, rs1861647, rs2242446, and rs36029) on cardiovascular and subjective stimulation after MDMA administration in 124 healthy subjects in a pooled analysis of eight double-blind, placebo-controlled studies. RESULTS:Carriers of the GG genotype of the SLC6A2 rs1861647 SNP presented higher elevations of heart rate and rate-pressure product after MDMA than subjects with one or no G alleles. Subjects with a C allele in the SLC6A2 rs2242446 SNP presented higher elevations of the heart rate after MDMA administration compared with the TT genotype. Subjects with the AA genotype of the SLC6A2 rs36029 SNP presented higher elevations of mean arterial pressure and rate pressure product after MDMA administration than carriers of the G allele. The SLC6A2 rs168924 and rs47958 SNPs did not alter the response to MDMA. CONCLUSIONS:Genetic polymorphisms of the SLC6A2 gene weakly moderated the acute cardiovascular response to MDMA in controlled studies and may play a minor role in adverse cardiovascular events when MDMA is used recreationally.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Vizeli P,Meyer Zu Schwabedissen HE,Liechti ME

doi

10.1007/s00228-017-2392-2

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

275-283

issue

3

eissn

0031-6970

issn

1432-1041

pii

10.1007/s00228-017-2392-2

journal_volume

74

pub_type

临床试验,杂志文章,随机对照试验

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