British Journal of Pharmacology
March 3, 2010
James R. Docherty, Ar Green
88 citations
Hyperthermia is a well-known acute adverse effect of MDMA (ecstasy) use, but the drug's influence on body temperature is complex, involving actions on serotonin, dopamine, and noradrenaline systems. In laboratory animals, MDMA can cause either hyperthermia or hypothermia depending on ambient temperature, through central thermoregulation and peripheral changes in blood flow and heat generation. Serotonin receptors modulate the hyperthermic response, while dopamine and noradrenaline systems also contribute—noradrenaline activates receptors that constrict skin blood vessels and increase heat production in brown fat. Hyperthermia in recreational users can be fatal, and no single drug is likely to reverse it; careful body cooling remains the main treatment. Educating users about ambient temperature control is key to prevention.
British Journal of Pharmacology
February 20, 2006
Sotiria Bexis, James R. Docherty
62 citations
In conscious rats, the amphetamine derivatives MDMA, MDA, and MDEA (each at 20 mg/kg) affected blood pressure, heart rate, body temperature, and movement. MDA caused the largest and most prolonged rise in blood pressure, accompanied by a slowed heart rate, while MDEA produced a brief, non-significant drop in diastolic pressure. All three initially lowered core body temperature, but MDA later caused a rise in temperature, with recovery speed fastest for MDA, then MDMA, then MDEA. Blocking α2A-adrenoceptors with BRL 44408 prolonged MDMA's hypothermic effect and triggered increased movement only with MDMA. In isolated rat aorta and vas deferens, the drugs' potency for contraction matched MDA > MDMA > MDEA, with MDEA acting as an antagonist.
British Journal of Pharmacology
November 1, 1999
Aisling Lavelle, Valerie Honner, James R. Docherty
55 citations
MDMA (ecstasy) acts as an agonist at alpha-2 adrenoceptors in the rat peripheral nervous system, inhibiting noradrenaline release and nerve-stimulated contractions. In atrial slices, MDMA (10 µM) reduced tritium release evoked by electrical stimulation, an effect blocked by the alpha-2 antagonist yohimbine. In the epididymal vas deferens, MDMA inhibited contractions with a pD2 of 5.88, antagonized by yohimbine but not by a serotonin receptor antagonist. In the prostatic vas deferens, yohimbine converted MDMA's inhibition into potentiation of contractions. Radioligand binding showed MDMA had similar affinities for alpha-2B, alpha-2C, and alpha-2D adrenoceptor subtypes, with pKi values around 5.1–5.3.
British Journal of Pharmacology
June 1, 2001
John Mcdaid, James R. Docherty
46 citations
MDMA (ecstasy) raises diastolic blood pressure in rats through multiple adrenoceptor mechanisms. In pithed rats, MDMA's pressor effects were blocked by α₁-adrenoceptor antagonist prazosin, α₂-antagonists yohimbine and methoxyidazoxan, and the non-selective 5-HT antagonist methiothepin, but not by the 5-HT₂ antagonist ritanserin. In anesthetized rats, MDMA produced a triphasic blood pressure response: an initial pressor phase involving α₂- and possibly α₁-adrenoceptors and 5-HT₂ receptors; a pressor component at 1 minute mediated largely by α₁-adrenoceptors; and a sustained depressor phase involving α₂-adrenoceptors and noradrenaline reuptake. The depressor response was most reduced by combining methoxyidazoxan and cocaine.
British Journal of Pharmacology
July 18, 2005
Sotiria Bexis, James R. Docherty
43 citations
MDMA produces complex effects on body temperature, including both hypothermia and hyperthermia, depending on ambient temperature and species. This study in mice found that MDMA acts as an α₂-adrenoceptor agonist. The α₂-adrenoceptor agonist clonidine caused hypothermia in wild-type mice but not in mice lacking the α₂A-adrenoceptor. MDMA alone caused significant hyperthermia in wild-type mice, but a biphasic response (hypothermia followed by hyperthermia) in knockout mice. Blocking the α₂A-adrenoceptor in wild-type mice before MDMA resulted in initial hypothermia. Thus, MDMA's α₂A-adrenoceptor agonist actions surprisingly shift the body temperature response from biphasic to monophasic hyperthermia.
British Journal of Pharmacology
April 30, 2009
Sotiria Bexis, James R. Docherty
36 citations
In conscious mice, the drug MDMA (20 mg/kg) caused a slow rise in body temperature peaking at 1.8°C above baseline about 130 minutes after injection. A low dose of the β3-adrenoceptor antagonist SR59230A (0.5 mg/kg) slightly reduced this hyperthermia. A high dose of SR59230A (5 mg/kg) instead triggered an early drop in temperature, an effect also produced by the α1-adrenoceptor blocker prazosin. Further tests showed that SR59230A also blocks α1-adrenoceptors. Thus, SR59230A alters MDMA's temperature effects mainly by blocking α1-adrenoceptors, which unmasks a hypothermic response, and to a lesser extent by possibly blocking β3-adrenoceptors to slightly reduce later hyperthermia.