No major role of norepinephrine transporter gene variations in the cardiostimulant effects of MDMA.
- Vizeli P Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, Department of Clinical Research, University Hospital Basel, University of Basel, Schanzenstrasse 55, 4056, Basel, Switzerland.
- Meyer Zu Schwabedissen HE Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
- Liechti ME Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, Department of Clinical Research, University Hospital Basel, University of Basel, Schanzenstrasse 55, 4056, Basel, Switzerland. matthias.liechti@usb.ch.
- 2017-12-04
Published in:
- European journal of clinical pharmacology. - 2018
Cardiostimulation
MDMA
Norepinephrine transporter
Pharmacogenetics
SLC6A2
Adolescent
Adrenergic Uptake Inhibitors
Adult
Alleles
Blood Pressure
Cardiotoxins
Cardiovascular Physiological Phenomena
Cross-Over Studies
Double-Blind Method
Female
Gene Frequency
Genetic Association Studies
Heart Rate
Heterozygote
Humans
Illicit Drugs
Male
N-Methyl-3,4-methylenedioxyamphetamine
Norepinephrine Plasma Membrane Transport Proteins
Pharmacogenetics
Polymorphism, Single Nucleotide
Psychotropic Drugs
Switzerland
Young Adult
English
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.
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1007/s00228-017-2392-2
- PMID 29198060
- Persistent URL
- https://sonar.ch/global/documents/232216
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