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Induction of malignant hyperthermia in susceptible swine by 3,4-methylenedioxymethamphetamine ("ecstasy").

Marko Fiege, Frank Wappler, Ralf Weisshorn, Mark U Gerbershagen, Melanie Menge, Jochen Schulte Am Esch

Anesthesiology November 2003 DOI: 10.1097/00000542-200311000-00020 (opens in new tab)

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Characteristics Controlled experimental animal study Peer reviewed
Sample size 12
Population MH-susceptible and MH-normal swine
Interventions MDMA Dantrolene Sodium bicarbonate Hyperventilation with 100% oxygen
Dose cumulative doses of 0.5, 1, 2, 4, 8, and 12 mg/kg
Topics MDMA
Key findings MDMA triggered malignant hyperthermia in all six genetically susceptible swine at 8 mg/kg, while MH-normal swine showed only moderate hypermetabolic changes even at 12 mg/kg. Dantrolene partially counteracted the clinical signs immediately. The authors conclude that MDMA induces MH in susceptible swine and that MH-susceptible patients should avoid MDMA or related drugs.

Abstract

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") can mediate acute toxic effects such as muscle rigidity, metabolic acidosis, and hyperthermia. Because of close clinical similarities, an association between MDMA intoxication and malignant hyperthermia (MH) was suggested. The aim of this study was to investigate whether MDMA is a trigger of MH in susceptible swine. MH-nontriggering general anesthesia was performed in six MH-susceptible (MHS) and six MH-normal swine. The animals were exposed to MDMA in cumulative doses of 0.5, 1, 2, 4, 8, and 12 mg/kg. The clinical occurrence of MH was defined by achievement of two of three conditions: central venous Pco2 >/=75 mmHg, central venous pH = 7.20, and increase of body core temperature >/= 2.0 degrees C. Once MH occurred, a standardized therapy with dantrolene, sodium bicarbonate, and hyperventilation with 100% oxygen was initialized. Administration of 8 mg/kg MDMA triggered MH in all MHS swine. The MH-normal swine also developed clinical signs of hypermetabolism, but even after administration of 12 mg/kg MDMA, changes were moderate compared with the MHS swine. Dantrolene therapy of MDMA-induced MH crisis in the MHS swine partially counteracted the clinical signs of MH immediately. MDMA induces MH in genetically susceptible swine in relevant doses. Therefore, MHS patients should avoid use of MDMA or related drugs. Patients with a personal or family history of MDMA-induced hyperthermia should be tested for a diagnosis of MH susceptibility. Dantrolene is effective in therapy of MDMA-induced porcine MH.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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