3,4-Methylenedioxymethamphetamine induces a hyperthermic and hypermetabolic crisis in pigs with and without a genetic disposition for malignant hyperthermia

Schütte, Jan Karl; Schäfer, Ute; Becker, Sandra; Oldewurtel, Christiane; Starosse, Alexander; Singler, Peter; Richard, Annette; Wappler, Frank; Gerbershagen, Mark U.

doi:10.1097/eja.0b013e32835a1127

Cited by 7 publications

(5 citation statements)

References 33 publications

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“…Similar to what has been observed with MDMA toxicity in rodent models, MH susceptible adrenalectomized pigs were also more resistant to MH toxicity, 109 and treatment with thyroid hormone led to an earlier onset of MH in pigs, 110 implicating activation of the hypothalamic-pituitary-adrenal and -thyroid axes in MH. Despite the similarities, a recent study done by Schutte et al 111 . to investigate whether MDMA could trigger MH in susceptible pigs found that there were no metabolic differences between MH-susceptible pigs and MH-normal pigs following MDMA exposure.…”

Section: Ucp Hyperthermia Versus Ryr1 “Malignant Hyperthermia”mentioning

confidence: 98%

The heat is on: Molecular mechanisms of drug-induced hyperthermia

2014

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Thermoregulation is an essential homeostatic process in which critical mechanisms of heat production and dissipation are controlled centrally in large part by the hypothalamus and peripherally by activation of the sympathetic nervous system. Drugs that disrupt the components of this highly orchestrated multi-organ process can lead to life-threatening hyperthermia. In most cases, hyperthermic agents raise body temperature by increasing the central and peripheral release of thermoregulatory neurotransmitters that ultimately lead to heat production in thermogenic effector organs skeletal muscle (SKM) and brown adipose tissue (BAT). In many cases hyperthermic drugs also decrease heat dissipation through peripheral changes in blood flow. Drug-induced heat production is driven by the stimulation of mechanisms that normally regulate the adaptive thermogenic responses including both shivering and non-shivering thermogenesis (NST) mechanisms. Modulation of the mitochondrial electrochemical proton/pH gradient by uncoupling protein 1 (UCP1) in BAT is the most well characterized mechanism of NST in response to cold, and may contribute to thermogenesis induced by sympathomimetic agents, but this is far from established. However, the UCP1 homologue, UCP3, and the ryanodine receptor (RYR1) are established mediators of toxicant-induced hyperthermia in SKM. Defining the molecular mechanisms that orchestrate drug-induced hyperthermia will be essential in developing treatment modalities for thermogenic illnesses. This review will briefly summarize mechanisms of thermoregulation and provide a survey of pharmacologic agents that can lead to hyperthermia. We will also provide an overview of the established and candidate molecular mechanisms that regulate the actual thermogenic processes in heat effector organs BAT and SKM.

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Section: Ucp Hyperthermia Versus Ryr1 “Malignant Hyperthermia”mentioning

confidence: 98%

The heat is on: Molecular mechanisms of drug-induced hyperthermia

2014

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“…In addition, dantrolene is used in case of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') overdose too [18]. Notably, there is already one published trial on successful DSS use in MDMA overdose in swine [19]. Further trials would be eligible.…”

Section: Expert Opinionmentioning

confidence: 99%

Do we foresee new emerging drugs to treat malignant hyperthermia?

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Gerbershagen

Grensemann

et al. 2015

Expert Opinion on Emerging Drugs

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“…booster or high doses)Green et al (2004);Parrott (2012);Schütte et al (2013);Topp et al (1999) Prolonged and vigorous dancing in hot settings during "rave" dance partiesDafters (1995); Docherty and Green (2010); Kiyatkin et al (2014); Parrott et al (2006); Suy et al (1999); Winstock et al (2001) Reduced fluid intake and dehydration Bouchama and Knochel (2002); Coris et al (2004); Montain and Coyle (1992); Sawka (1992); Sawka et al (1985) Co-use of MDMA and alcohol Calle et al (2019); Calle et al (2018); Horyniak et al (2014); Liechti et al (2005); Palamar et al (2019); Rogers et al (2009); Roxburgh and Lappin (2020); Schifano (2004); Schifano et al (2003) Hyperthyroidism Sprague et al (2018)…”

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confidence: 99%

Hard Boiled: Alcohol Use as a Risk Factor for MDMA-Induced Hyperthermia: a Systematic Review

et al. 2021

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Although MDMA (ecstasy) is a relatively safe recreational drug and is currently considered for therapeutic use for the treatment of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), recreational MDMA use occasionally elicits hyperthermia and hyponatremia, sometimes with a fatal outcome. Specific risk factors for both adverse effects are profuse sweating while vigorously dancing under unfavorable conditions such as high ambient temperatures and insufficient fluid suppletion which result in dehydration. Concomitant use of MDMA and alcohol is highly prevalent, but adds to the existing risk, because alcohol facilitates the emergence of MDMA-induced adverse events, like hyperthermia, dehydration, and hyponatremia. Because of potential health-related consequences of concomitant use of MDMA and alcohol, it is important to identify the mechanisms of the interactions between alcohol and MDMA. This review summarizes the main drivers of MDMA-induced hyperthermia, dehydration, and hyponatremia and the role of concomitant alcohol use. It is shown that alcohol use has a profound negative impact by its interaction with most of these drivers, including poikilothermia, exposure to high ambient temperatures, heavy exercise (vigorous dancing), vasoconstriction, dehydration, and delayed initiation of sweating and diuresis. It is concluded that recreational and clinical MDMA-users should refrain from concomitant drinking of alcoholic beverages to reduce the risk for adverse health incidents when using MDMA.

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3,4-Methylenedioxymethamphetamine induces a hyperthermic and hypermetabolic crisis in pigs with and without a genetic disposition for malignant hyperthermia

Cited by 7 publications

References 33 publications

The heat is on: Molecular mechanisms of drug-induced hyperthermia

The heat is on: Molecular mechanisms of drug-induced hyperthermia

Do we foresee new emerging drugs to treat malignant hyperthermia?

Hard Boiled: Alcohol Use as a Risk Factor for MDMA-Induced Hyperthermia: a Systematic Review

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