No major role of norepinephrine transporter gene variations in the cardiostimulant effects of MDMA
Patrick Vizeli, Henriette E. Meyer zu Schwabedissen, Matthias E. Liechti
European Journal of Clinical Pharmacology December 2, 2017 DOI: 10.1007/s00228-017-2392-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pooled analysis of eight double-blind, placebo-controlled studies Peer reviewed |
|---|---|
| Sample size | 124 |
| Population | Healthy subjects |
| Intervention | MDMA |
| Topics | MDMA |
| Keywords | Norepinephrine transporter Pharmacology Gene Endocrinology Dopamine Biochemistry |
| Citations | 15 |
| Key points | Genetic polymorphisms of the SLC6A2 gene weakly moderate the acute cardiovascular response to MDMA, with specific SNPs associated with higher heart rate and blood pressure elevations. |
Abstract
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 α 1 -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. 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. 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. 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.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
Citations in the library
Cited by 11
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies Journal of Psychopharmacology March 30, 2021
- MDMA interactions with pharmaceuticals and drugs of abuse Expert Opinion on Drug Metabolism & Toxicology March 31, 2020
- Cellular Uptake of Psychostimulants – Are High- and Low-Affinity Organic Cation Transporters Drug Traffickers? Frontiers in Pharmacology January 20, 2021
- Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms. European Journal of Pharmacology May 7, 2021
and 6 more in the library
Cites 23
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and 18 more in the library