Metabolism of the recently encountered designer drug, methylone, in humans and rats

Abstract

The urinary metabolites of methylone in humans and rats were investigated by analysing urine specimens from its abuser and after administrating to rats with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS), using authentic standards. The time-course excretion profiles of methylone and its three metabolites in rats were further investigated after a single intraperitoneal dosing of 5 mg kg-1 methylone hydrochloride. Two major metabolic pathways were revealed for both humans and rats as follows: (1) side-chain degradation by N-demethylation to the corresponding primary amine methylenedioxycathinone (MDC), partly conjugated; and (2) demethylenation followed by O-methylation of either a 3- or 4-OH group on the benzene ring to produce 4-hydroxy-3-methoxymethcathinone (HMMC) or 3-hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MC), respectively, mostly conjugated. Of these metabolites, HMMC was the most abundant in humans and rats. The cumulative amount of urinary HMMC excreted within the first 48 h in rats was approximately 26% of the dose, and the amount of the parent methylone was not more than 3%. These results demonstrate that the analysis of HMMC will be indispensable for proof of the use of methylone in forensic urinalysis.

Seizures and Hyponatremia Related to Ethcathinone and Methylone Poisoning

“…Methylone increases the concentration of monoamine neurotransmitters such as serotonin, dopamine and noradrenaline in the human synaptic cleft, through inhibition of plasma membrane monoamine reuptake transporters [3]. Methylone acts as a stimulant of the central nervous system and has some hallucinogenic effects.…”

“…Methylone is marketed on the internet as a high-purity plant food, which can give false confidence to teenagers and young adults attracted to stimulants similar to ecstasy (Figs. 1, 2, 3) [3].…”

An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as “bath salts”

“…To our knowledge, all published papers on pharmacokinetics of methylone are of a forensic nature (urinary collected specimens) (Crawse et al, 2012, Kamata et al, 2006 or from in vitro experiments (Mueller and Rentsch, 2012). This study constitutes the first approach to the kinetics of methylone based on in vivo blood sample data from laboratory animals and will be helpful to…”

“…Some reports describe that in humans the onset of effect of methylone appears at 15-30 min with a 2-3.5 h duration, but 6-24 h to return to "normal" status. Kamata et al (2006) identified the characteristic human and rat urinary metabolites of methylone that were of great importance in forensic analysis (Zaitsu et al, 2009). Moreover, some human sudden deaths related to methylone intake have been reported (Cawrse et al, 2012, Pearson et al, 2012 and some reported cases met the Hunter criteria for serotonin syndrome (Boyer andShannon, 2005, Warrick et al, 2012).…”

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

“…Kamata et al (2006) first evaluated methylone metabolism by determining parent and metabolite concentrations in urine from rats and humans exposed to methylone. These investigators showed that methylone is metabolized in a manner akin to MDMA involving two major pathways ( Figure 1): (1) O-demethylenation to form ( ± )-3,4-dihydroxy-N-methylcathinone (HHMC) followed by O-methylation to form ( ± )-4-hydroxy-3-methoxy-N-methylcathinone (HMMC) and (2) N-demethylation to produce ( ± )-3,4-methylenedioxycathinone (MDC) (Kamata et al, 2006). Methylone is primarily biotransformed by cytochrome p450 2D6 (CYP2D6) in humans, the same isoform responsible for metabolism of MDMA (Pedersen et al, 2013).…”