Lethal Serotonin Syndrome After Methylone and Butylone Ingestion

Warrick, Brandon J.; Wilson, John W.; Hedge, Matthew; Freeman, Scott B; Léonard, Karen; Aaron, Cynthia K.

doi:10.1007/s13181-011-0199-6

Cited by 137 publications

(49 citation statements)

References 6 publications

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“…Despite these legislative efforts, reports by the DEA revealed that the prevalence of methylone increased from 2011 to 2013, and as of 2014, methylone was encountered as often as the club drug 3,4-methylenedioxy-N-methylamphetamine (MDMA) (NFLIS Special Report, 2014;NFLIS 2014 Annual Report). Recreational users take methylone for its euphoric and stimulant properties, but it can cause life-threatening adverse effects, including hyperthermia, seizures, and kidney damage; its use has led to several analytically confirmed fatalities (Barrios et al, 2015;Carbone et al, 2013;Cawrse et al, 2012;Kovacs et al, 2012;Ridpath et al, 2014;Warrick et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats

Elmore

Dillon‐Carter

Partilla

et al. 2016

Neuropsychopharmacol

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3,4-Methylenedioxy-N-methylcathinone (methylone) is a new psychoactive substance and the β-keto analog of 3,4-methylenedioxy-Nmethylamphetamine (MDMA). It is well established that MDMA metabolism produces bioactive metabolites. Here we tested the hypothesis that methylone metabolism in rats can form bioactive metabolites. First, we examined the pharmacokinetics (PKs) of methylone and its metabolites after subcutaneous (sc) methylone administration (3, 6, 12 mg/kg) to male rats fitted with intravenous (iv) catheters for repeated blood sampling. Plasma specimens were assayed by liquid chromatography tandem mass spectrometry to quantify methylone and its phase I metabolites: 3,4-methylenedioxycathinone (MDC), 3,4-dihydroxy-N-methylcathinone (HHMC), and 4-hydroxy-3-methoxy-Nmethylcathinone (HMMC). The biological activity of methylone and its metabolites was then compared using in vitro transporter assays and in vivo microdialysis in rat nucleus accumbens. For the PK study, we found that methylone and MDC peaked early (T max = 15-45 min) and were short lived (t 1/2 = 60-90 min), while HHMC and HMMC peaked later (T max = 60-120 min) and persisted (t 1/2 = 120-180 min). Areaunder-the-curve values for methylone and MDC were greater than dose-proportional, suggesting non-linear accumulation. Methylone produced significant locomotor activation, which was correlated with plasma methylone, MDC, and HHMC concentrations. Methylone, MDC, and HHMC were substrate-type releasers at monoamine transporters as determined in vitro, but only methylone and MDC (1, 3 mg/kg, iv) produced significant elevations in brain extracellular dopamine and 5-HT in vivo. Our findings demonstrate that methylone is extensively metabolized in rats, but MDC is the only centrally active metabolite that could contribute to overall effects of the drug in vivo.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats

Elmore

Dillon‐Carter

Partilla

et al. 2016

Neuropsychopharmacol

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“…Being thermolabile, they are probably not smokable. Since mid-2010, cathinones have been circulating under their proper names, but sometimes sold as ecstasy (methylenedioxymethamphetamine (MDMA)) or amphetamines [6]. In France, all cathinone derivatives have been classified as narcotics since the 27th of July 2012.…”

Section: Introductionmentioning

confidence: 99%

Death following ingestion of methylone

Barrios¹,

Grison-Hernando

Boels

et al. 2015

Int J Legal Med

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Methylone is a synthetic derivative of cathinone. It is sold principally on the Internet in powder form under the name «bath salts». Deaths following consumption are very rare. This report details the first case of a death in France (a 21-year-old man), following ingestion of methylone during an evening with friends. Anoxia was observed at the time of autopsy. Toxicological analyses highlighted a consumption of methylone and cannabis. However, biological analyses showed an absence of ethanol, cocaine, amphetamines, and opiate derivatives. Likewise, no medications were found. High concentrations of methylone were found in the peripheral blood (3.13 mg/L) and in the central blood (6.64 mg/L). Its presence in the gastric contents provides evidence that the substance was taken orally. The dosage of δ9-tetrahydrocannabinol (THC) suggests a recent cannabis consumption (THC 12.9 μg/L, THC-COOH 29.3 μg/L, 11-OH-THC 4.9 μg/L). This case illustrates that the consumption of methylone, which has a reputation of being less «powerful» than ecstasy, is not without its dangers.

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“…Deaths have been associated with a range of synthetic cathinones, including: mephedrone [87,88,90,101,102], methylone and butylone [103], ethylone [104], bupropion [82], α-PVP [95,105,106], MDPV [93,[107][108][109], and methedrone [110].…”

Section: Deathsmentioning

confidence: 99%

NPS: Medical Consequences Associated with Their Intake

Schifano

Orsolini

Papanti

et al. 2016

Current Topics in Behavioral Neurosciences

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Over the last decade, the 'traditional' drug scene has been supplemented - but not replaced - by the emergence of a range of novel psychoactive substances (NPS), which are either newly created or existing drugs, including medications, now being used in novel ways. By the end of 2014, in excess of 500 NPS had been reported by a large number of countries in the world. Most recent data show, however, that synthetic cathinones, synthetic cannabinoids, and psychedelics/phenethylamines account for the largest number of NPS.The present chapter aims at providing an overview of the clinical and pharmacological issues relating to these most popular NPS categories. Given the vast range of medical and psychopathological issues associated with the molecules here described, it is crucial for health professionals to be aware of the effects and toxicity of NPS. A general overview of the acute management of NPS adverse events is provided as well, although further studies are required to identify a range of evidence-based, index molecule-focused, treatment strategies. The rapid pace of change in the NPS online market constitutes a major challenge to the provision of current and reliable scientific knowledge on these substances.

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Lethal Serotonin Syndrome After Methylone and Butylone Ingestion

Cited by 137 publications

References 6 publications

Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats

Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats

Death following ingestion of methylone

NPS: Medical Consequences Associated with Their Intake

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