The role of the sympathetic nervous system and uncoupling proteins in the thermogenesis induced by 3,4-methylenedioxymethamphetamine

Edward M. Mills, Daniel E. Rusyniak, Jon E. Sprague

Research output: Contribution to journalReview article

59 Scopus citations


Body temperature regulation involves a homeostatic balance between heat production and dissipation. Sympathetic agents such as 3,4- methylenedioxymethamphetamine (MDMA, ecstasy) can disrupt this balance and as a result produce an often life-threatening hyperthermia. The hyperthermia induced by MDMA appears to result from the activation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-thyroid/adrenal axis. Norepinephrine release mediated by MDMA creates a double-edged sword of heat generation through activation of uncoupling protein (UCP3) along with α 1- and β 3-adrenoreceptors and loss of heat dissipation through SNS-mediated vasoconstriction. This review examines cellular mechanisms involved in MDMA-induced thermogenesis from UCP activation to vasoconstriction and how these mechanisms are related to other thermogenic conditions and potential treatment modalities.

Original languageEnglish (US)
Pages (from-to)787-799
Number of pages13
JournalJournal of Molecular Medicine
Issue number12
StatePublished - Dec 1 2004



  • 3,4-Methylenedioxymethamphetamine
  • Hyperthermia
  • Rhabdomyolysis
  • UCP-3
  • Uncoupling proteins

ASJC Scopus subject areas

  • Medicine(all)

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