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

J Mol Med (Berl). 2004 Dec;82(12):787-99. doi: 10.1007/s00109-004-0591-7. Epub 2004 Nov 10.


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 alpha1- and beta3-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.

Publication types

  • Review

MeSH terms

  • Animals
  • Body Temperature / drug effects
  • Body Temperature / physiology*
  • Carrier Proteins / metabolism
  • Fever / chemically induced
  • Fever / metabolism
  • Fever / physiopathology
  • Hallucinogens / pharmacology*
  • Humans
  • Ion Channels
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondrial Proteins
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Sympathetic Nervous System / drug effects*
  • Uncoupling Protein 3


  • Carrier Proteins
  • Hallucinogens
  • Ion Channels
  • Mitochondrial Proteins
  • UCP3 protein, human
  • Uncoupling Protein 3
  • N-Methyl-3,4-methylenedioxyamphetamine