Cardiac effects of MDMA on the metabolic profile determined with 1H‐magnetic resonance spectroscopy in the rat
Shane A. Perrine, Mark S. Michaels, Farhad Ghoddoussi, Elisabeth Hyde, Manuel E. Tancer, Matthew P. Galloway
NMR in Biomedicine November 4, 2008 DOI: 10.1002/nbm.1352 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | MDMA |
| Dose | 0, 5, or 10 mg/kg every 2 h for a total of four injections |
| Duration | 8 h drug exposure, sacrificed 2 h after last injection |
| Topics | MDMA Serotonin |
| Keywords | Creatine Choline Heart rate Taurine Pharmacology Endocrinology |
| Citations | 39 |
| Key findings | MDMA dose-dependently increased body temperature, decreased cardiac serotonin levels, increased carnitine, and decreased choline in rat heart tissue, indicating disruption of cardiac metabolic homeostasis. |
Abstract
Abstract Despite the potential for deleterious (even fatal) effects on cardiac physiology, 3,4‐methylenedioxymethamphetamine (MDMA; ecstasy) abuse abounds driven mainly by its euphoric effects. Acute exposure to MDMA has profound cardiovascular effects on blood pressure and heart rate in humans and animals. To determine the effects of MDMA on cardiac metabolites in rats, MDMA (0, 5, or 10 mg/kg) was injected every 2 h for a total of four injections; animals were sacrificed 2 h after the last injection (8 h drug exposure), and their hearts removed and tissue samples from left ventricular wall dissected. High resolution magic angle spinning proton magnetic resonance spectroscopy ( 1 H‐MRS) at 11.7 T, a specialized version of MRS aptly suited for analysis of semi‐solid materials such as intact tissue samples, was used to measure the cardiac metabolomic profile, including alanine, lactate, succinate, creatine, and carnitine, in heart tissue from rats treated with MDMA. MDMA effects on MR‐visible choline, glutamate, glutamine, and taurine were also determined. Body temperature was measured following each MDMA administration and serotonin and norepinephrine (NE) levels were measured by high pressure liquid chromatography (HPLC) in heart tissue from treated animals. MDMA significantly and dose‐dependently increased body temperature, a hallmark of amphetamines. Serotonin, but not NE, levels were significantly and dose‐dependently decreased by MDMA in the heart wall. MDMA significantly altered the MR‐visible profile with an increase in carnitine and no change in other key compounds involved in cardiomyocyte energy metabolomics. Finally, choline levels were significantly decreased by MDMA in heart. The results are consistent with the notion that MDMA has significant effects on cardiovascular serotonergic tone and disrupts the metabolic homeostasis of energy regulation in cardiac tissue, potentially increasing utilization of fatty acid metabolism. The contributions of serotonergic signaling on MDMA‐induced changes in cardiac metabolism remain to be determined. Copyright © 2008 John Wiley & Sons, Ltd.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 6
- Comparative Untargeted Metabolomics Analysis of the Psychostimulants 3,4-Methylenedioxy-Methamphetamine (MDMA), Amphetamine, and the Novel Psychoactive Substance Mephedrone after Controlled Drug Administration to Humans Metabolites July 27, 2020
- Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms. European Journal of Pharmacology May 7, 2021
- First Time View on Human Metabolome Changes after a Single Intake of 3,4-Methylenedioxymethamphetamine in Healthy Placebo-Controlled Subjects Journal of Proteome Research July 19, 2017
- MDMA Induced Cardio-toxicity and Pathological Myocardial Effects: A Systematic Review of Experimental Data and Autopsy Findings. Cardiovascular toxicology December 2019
- GC-MS metabolomics reveals disturbed metabolic pathways in primary mouse hepatocytes exposed to subtoxic levels of 3,4-methylenedioxymethamphetamine (MDMA). Archives of Toxicology November 2018
and 1 more in the library
Cites 11
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. Journal of Pharmacology and Experimental Therapeutics July 1, 1999
- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Clinical Studies Neuropsychobiology 2000
- Cardiovascular Effects of 3,4-Methylenedioxymethamphetamine: A Double-Blind, Placebo-Controlled Trial Annals of Internal Medicine December 19, 2000
- Metabolism Is Required for the Expression of Ecstasy-Induced Cardiotoxicity in Vitro Chemical Research in Toxicology April 27, 2004
and 6 more in the library