Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography–mass spectrometry

Meyer, Markus R.; Wilhelm, J.; Peters, Frank T.; Maurer, Hans H.

doi:10.1007/s00216-010-3636-5

Cited by 254 publications

(174 citation statements)

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“…Meyer et al (2010) suggested the most probable metabolites of mephedrone present in the urine. In this study mephedrone was administered orally and urine was collected over a 24-hour period.…”

Section: Introductionmentioning

confidence: 99%

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

et al. 2013

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Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine.Objective The major aims were to investigate the pharmacokinetics and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. MethodsMephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized by LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min.Results Mephedrone plasma concentrations after i.v. administration fit to a twocompartment model (α=10.23 h -1 and β=1.86 h -1 ). After oral administration, peak mephedrone concentrations were achieved between 0.5-1 h, and declined to undetectable levels at 9 h. Absolute bioavailability of mephedrone was of about 10% and the percentage of mephedrone protein binding was of 21.59 ± 3.67%. We have identified five Phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85 ± 0.08.Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. ConclusionsWe suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

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Section: Introductionmentioning

confidence: 99%

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

et al. 2013

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“…It is also a drug of the amphetamine [7] class and a chemical derivative of cathinone that is progressively entering the recreational drug market [8]. It mainly acts as a moderately potent noradrenaline releasing agent, with relatively weak inhibition of dopamine and serotonin reuptake.…”

Section: Discussionmentioning

confidence: 99%

Seizures and Hyponatremia Related to Ethcathinone and Methylone Poisoning

et al. 2011

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Introduction We report a case of ethcathinone and methylone poisoning with severe clinical toxicity. This is to our knowledge the first case reported in the medical toxicology literature. Case Report A 22-year-old woman was brought to the emergency department following several episodes of tonicoclonic seizures, a few hours after ingesting "legal ecstasy". The patient needed intubation for recurrent seizures, and she was found to have severe hyponatremia (120 mmol/L) that was corrected with hypertonic saline. The patient's mental status improved rapidly, and she was extubated the day following her admission. However, she developed prolonged rhabdomyolysis (CK 34.537 U/L) that required a 6-day hospitalisation. Discussion The seizures and the hyponatremia may be explained by the MDMA-like characteristics of methylone that may induce inappropriate secretion of antidiuretic hormone mediated via the serotonin system. The combination of methylone and ethcathinone (both acting like serotonin reuptake inhibitors) might have contributed to neurologic manifestations compatible with serotonin toxicity, although our patient never had autonomic instability. Our patient had a prolonged period of rhabdomyolysis which may also be explained by excessive serotonin activity resulting in an increased motor hyperactivity. The public has to be aware of this growing health problem. Clinicians must report future cases of toxicity related to the use of cathinone synthetic derivatives in order to increase our knowledge of these substances.

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“…Some of the alcohols are conjugated via sulfation or glucuronidation and excreted in the urine [56].…”

Section: Metabolism: Pyrovaleronementioning

confidence: 99%

The Toxicology of Bath Salts: A Review of Synthetic Cathinones

2011

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Synthetic cathinones have recently emerged and grown to be popular drugs of abuse. Their dramatic increase has resulted in part from sensationalized media attention as well as widespread availability on the Internet. They are often considered "legal highs" and sold as "bath salts" or "plant food" and labeled "not for human consumption" to circumvent drug abuse legislation. Cathinone is a naturally occurring beta-ketone amphetamine analogue found in the leaves of the Catha edulis plant. Synthetic cathinones are derivatives of this compound. Those that are being used as drugs of abuse include butylone, dimethylcathinone, ethcathinone, ethylone, 3-and 4-fluoromethcathinone, mephedrone, methedrone, methylenedioxypyrovalerone (MDPV), methylone, and pyrovalerone. Synthetic cathinones are phenylalkylamines derivatives, and are often termed "bk-amphetamines" for the beta-ketone moiety. They may possess both amphetaminelike properties and the ability to modulate serotonin, causing distinct psychoactive effects. Desired effects reported by users of synthetic cathinones include increased energy, empathy, openness, and increased libido. Cardiac, psychiatric, and neurological signs and symptoms are the most common adverse effects reported in synthetic cathinone users who require medical care. Deaths associated with use of these compounds have been reported. Exposure to and use of synthetic cathinones are becoming increasingly popular despite a lack of scientific research and understanding of the potential harms of these substances. The clinical similarities to amphetamines and MDMA specifically are predictable based on the chemical structure of this class of agents. More work is necessary to understand the mechanisms of action, toxicokinetics, toxicodynamics, metabolism, clinical and psychological effects as well as the potential for addiction and withdrawal of these agents.

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Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography–mass spectrometry

Cited by 254 publications

References 15 publications

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Seizures and Hyponatremia Related to Ethcathinone and Methylone Poisoning

The Toxicology of Bath Salts: A Review of Synthetic Cathinones

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