Attenuation of 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy)‐induced rhabdomyolysis with α1‐ plus β3‐adrenoreceptor antagonists

Sprague, Jon E.; Brutcher, Robert E.; Mills, Edward; Caden, David; Rusyniak, Daniel E.

doi:10.1038/sj.bjp.0705823

Cited by 47 publications

(43 citation statements)

References 26 publications

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“…In the same report, supplementation of adrenalectomized rats with corticosterone almost reinstated the immediate hyperthermic effect of MDMA [155]. Sprague-Dawley rats' concomitant pretreatment with both α 1 -adrenoreceptor plus β 3 -adrenoreceptor antagonists abolished MDMA-induced hyperthermia [156,170]. Also in rats, neither propranolol nor nadolol (nonselective β 1 -and β 2 -adrenoreceptor antagonists) when administered 30 min before MDMA affected the thermogenic response; in contrast, carvedilol (nonselective α 1 -and β-adrenoreceptor antagonist), either injected 15 min before or after MDMA, prevented its hyperthermic response [171].…”

Section: Role Of Adrenoreceptors In Mdma-induced Hyperthermiamentioning

confidence: 84%

Molecular and Cellular Mechanisms of Ecstasy-Induced Neurotoxicity: An Overview

et al. 2009

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"Ecstasy" [(+/-)-3,4-methylenedioxymethamphetamine, MDMA, XTC, X, E] is a psychoactive recreational hallucinogenic substance and a major worldwide drug of abuse. Several reports raised the concern that MDMA has the ability to induce neurotoxic effects both in laboratory animals and humans. Despite more than two decades of research, the mechanisms by which MDMA is neurotoxic are still to be fully elucidated. MDMA induces serotonergic terminal loss in rats and also in some mice strains, but also a broader neuronal degeneration throughout several brain areas such as the cortex, hippocampus, and striatum. Meanwhile, in human "ecstasy" abusers, there are evidences for deficits in seronergic biochemical markers, which correlate with long-term impairments in memory and learning. There are several factors that contribute to MDMA-induced neurotoxicity, namely, hyperthermia, monoamine oxidase metabolism of dopamine and serotonin, dopamine oxidation, the serotonin transporter action, nitric oxide, and the formation of peroxinitrite, glutamate excitotoxicity, serotonin 2A receptor agonism, and, importantly, the formation of MDMA neurotoxic metabolites. The present review covered the following topics: history and epidemiology, pharmacological mechanisms, metabolic pathways and the influence of isoenzyme genetic polymorphisms, as well as the acute effects of MDMA in laboratory animals and humans, with a special focus on MDMA-induced neurotoxic effects at the cellular and molecular level. The main aim of this review was to contribute to the understanding of the cellular and molecular mechanisms involved in MDMA neurotoxicity, which can help in the development of therapeutic approaches to prevent or treat the long-term neuropsychiatric complications of MDMA abuse in humans.

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Section: Role Of Adrenoreceptors In Mdma-induced Hyperthermiamentioning

confidence: 84%

Molecular and Cellular Mechanisms of Ecstasy-Induced Neurotoxicity: An Overview

et al. 2009

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“…It is important to note, however, that changes in UCP3 activity (which are not detected at the protein or gene level) may account for increased state 4 respiration and, therefore, contribute to postprandial thermogenesis. Indeed, UCP3 is essential for 3,4-methylenedioxymethamphetamine (MDMA or ecstasy)-induced hyperthermia (35), and this effect can be attenuated using ␤3-adrenoceptor antagonists (51). In addition to changes in UCP3, altered state 4 respiration in skeletal muscle mitochondria, may be driven by the adenine nucleotide translocase (ANT) (22); this warrants future investigation.…”

Section: Discussionmentioning

confidence: 98%

Postprandial heat production in skeletal muscle is associated with altered mitochondrial function and altered futile calcium cycling

Clarke

Lee

Andrews

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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This study aimed to determine whether postprandial temperature excursions in skeletal muscle are consistent with thermogenesis or altered blood flow. Temperature probes were implanted into the vastus lateralis muscle of ovariectomized ewes, and blood flow was assessed using laser-Doppler flowmetry (tissue flow) and transit-time ultrasound flowmetry (femoral artery flow). The animals were program-fed between 1100 and 1600, and temperature and blood flow were measured during intravenous administration of either isoprenaline or phenylephrine and during feeding and meal anticipation. In addition, muscle biopsies were collected prefeeding and postfeeding to measure uncoupling protein (UCP) expression and mitochondrial function, as well as indices of calcium cycling (ryanodine 1 receptor: RyR1 and sarcoendoplasmic calcium-dependent ATPases SERCA1/ SERCA2a). Isoprenaline increased femoral artery blood flow, whereas phenylephrine reduced blood flow. At high doses only, isoprenaline treatment increased heat production in muscle. Phenylephrine treatment did not alter muscle temperature. Meal anticipation was evoked in fasted animals (previously program-fed) that were housed beside animals that were fed. Increases in muscle temperature were elicited by feeding and meal anticipation, without changes in blood flow during either paradigm. Analyses of respiration in isolated mitochondria indicated that the postprandial increase in heat production was associated with an increase in state 4 respiration, without increased UCP1, UCP2, or UCP3 expression. Feeding increased the expression of RyR1 and SERCA2a. We conclude that excursions in muscle temperature may occur independent of blood flow, suggesting that postprandial heat production is driven by altered mitochondrial function and changes in calcium cycling.

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“…The 4-hr time point was used because we have previously shown that CK levels peak at this time point following a hyperthermic dose of MDMA (20). These blood samples were collected from six MDMAvehicle and six MDMA-carvedilol animals 60 mins post-MDMA administration.…”

Section: Creatine Kinase (Ck) Measurementmentioning

confidence: 99%