Sympathomimetic Actions of Methylenedioxymethamphetamine in Rat and Rabbit Isolated Cardiovascular Tissues
J L Fitzgerald, J J Reid
Journal of Pharmacy and Pharmacology October 1, 1994 DOI: 10.1111/j.2042-7158.1994.tb03738.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro pharmacological study in isolated animal tissues Peer reviewed |
|---|---|
| Population | Isolated cardiovascular tissues from rats (atria, perfused hearts) and rabbits (perfused and superfused ear arteries) |
| Interventions | MDMA Amphetamine Desipramine Propranolol Noradrenaline |
| Dose | 10 μm MDMA; 1 μm amphetamine; 1 μm desipramine; 1 μm propranolol; noradrenaline 10 and 50 nM |
| Measures | heart rate (chronotropic response), resting and stimulation-induced outflow of radioactivity, perfusion pressure, vasoconstrictor responses, dysrhythmias |
| Topics | MDMA |
| Key points | MDMA increased heart rate and noradrenaline release in isolated rat and rabbit cardiovascular tissues, effects blocked by the neuronal uptake inhibitor desipramine, and it induced dysrhythmias in 7 of 11 isolated rat hearts. The authors conclude MDMA has sympathomimetic activity similar to amphetamine, which they suggest could account for cardiovascular side-effects associated with its use. |
Abstract
Abstract: The aim of this study was to investigate the actions of methylenedioxymethamphetamine (MDMA) in several isolated cardiovascular tissues. In spontaneously beating rat atria, concentration-dependent positive chronotropic responses to MDMA and amphetamine were blocked by the neuronaluptake inhibitor desipramine (1 μm) and the β-adrenoceptor antagonist propranolol (1 μm). In atria incubated with [3H]noradrenaline to label transmitter stores, 10 μm MDMA and 1 μm amphetamine increased the resting outflow of radioactivity, while 1 μm desipramine had no effect on resting outflow. The MDMA- and amphetamine-induced release of radioactivity were blocked by 1 μm desipramine. MDMA, amphetamine and desipramine each enhanced the electrical stimulation-induced (2 Hz, 30-s train) release of radioactivity; the enhancing effects of MDMA and amphetamine were blocked by 1 μm desipramine. In rat isolated perfused hearts, MDMA (1 and 10 μm) increased heart rate by a similar amount to the increase caused by noradrenaline (10 and 50 Nm). MDMA also induced dysrhythmias in 7 out of 11 rat isolated perfused heart preparations. In rabbit isolated perfused and superfused ear arteries preloaded with [3H]noradrenaline, MDMA increased the resting release of radioactivity by 230 ± 18% (n = 6) of control resting release; the increase was accompanied by a rise in perfusion pressure of 17 ± 7 mmHg (n = 6). MDMA also facilitated the vasoconstrictor responses to noradrenaline (3–9 ng) and perivascular nerve stimulation (1–5 Hz, 10-s train). MDMA-induced vasoconstriction and the facilitation of vasoconstrictor responses to noradrenaline and electrical stimulation were blocked by 1 μm desipramine. These results suggest that MDMA has similar sympathomimetic activity to amphetamine on cardiovascular tissues. The sympathomimetic actions of MDMA could account for the cardiovascular side-effects associated with its use.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Cardiovascular Effects of 3,4-Methylenedioxymethamphetamine: A Double-Blind, Placebo-Controlled Trial Annals of Internal Medicine December 19, 2000
- The role of monoamines in the changes in body temperature induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives British Journal of Pharmacology March 3, 2010
- Metabolism Is Required for the Expression of Ecstasy-Induced Cardiotoxicity in Vitro Chemical Research in Toxicology April 27, 2004
- Effects of MDMA, MDA and MDEA on blood pressure, heart rate, locomotor activity and body temperature in the rat involveα‐adrenoceptors British Journal of Pharmacology February 20, 2006
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Cites 8
- 'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA JAMA March 27, 1987
- 'Eve' and 'Ecstasy' JAMA March 27, 1987
- Methylenedioxyamphetamine. Clinical description of overdose, death, and review of pharmacology Archives of Internal Medicine October 1, 1981
- Methylenedioxyamphetamine Archives of Internal Medicine October 1, 1981
- Human Deaths and Toxic Reactions Attributed to MDMA and MDEA Ecstasy: The Clinical, Pharmacological and Neurotoxicological Effects of the Drug MDMA 1990
and 3 more in the library