What is the role of dantrolene in the treatment of MDMA toxicity?

Updated: Dec 20, 2017
  • Author: In-Hei Hahn, MD, FACEP, FACMT; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD  more...
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Answer

Dantrolene (1 mg/kg or 80 mg intravenously [IV]) has been used for the treatment of hyperpyrexia after conventional therapy. Dantrolene is typically used to treat malignant hyperthermia, a genetic disorder of the skeletal muscle due to a defect in the ryanodine receptor that allows for massive release of calcium from the sarcoplasmic reticulum during exposures to general anesthetics.

MDMA-induced hyperthermia is thought to be centrally mediated via serotonin toxicity. Although the mechanism of dantrolene does not seem to correlate with what is known about MDMA-induced hyperthermia, dantrolene was first used to treat hyperthermia in the setting of MDMA-related hyperpyrexia in 1992 due to the similarity of presentation.

A systematic compilation of MDMA case reports suggests possible evidence of benefit in using dantrolene to treat hyperthermia. [27] The study showed decreased morbidity and mortality with rare side effects from the dantrolene itself, especially in patients who present with temperatures above 40°C, and particularly above 42°C. The biggest caveat with using case series and case reports is recognizing the limitations of reporting and publication biases.

A study in an animal model found that clozapine resulted in a marked and immediate reversal of MDMA-induced hyperthermia, via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia, and labetalol was ineffective. [28]


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