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

López-Arnau, Raúl; Martínez-Clemente, José; Carbó, Marcel·lí; Piccoli, David A.; Escubedo, Elena; Camarasa, Jorge

doi:10.1016/j.pnpbp.2013.04.007

Cited by 50 publications

(45 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This schedule is related with patterns used by humans and agree with methylone's half-life in rodents (López-Arnau et al, 2013). Following this, we found decrease in frontal cortex and hippocampal serotoninergic nerve ending markers around 20-25% together with hippocampal astrogliosis suggesting nerve ending injuries.…”

Section: Page 14 Of 29 Psychopharmacologysupporting

confidence: 86%

“…Accordingly, present experiments were carried out at a high ambient temperature simulating hot conditions found in dance clubs. We administered the drug at 3-3.5h interval, in accordance with our previous paper characterizing the pharmacokinetics of methylone, distinguished by its short half-life (López-Arnau et al, 2013). To model recreational methylone use, we simulated the widespread practices of "stacking" (taking multiple doses at once in order to increase the desired effect and/or offset tolerance from prior use) and "boosting" (taking supplemental doses over time in order to maintain the drug's effect).…”

Section: Depressant-like Effect Of Methylonementioning

confidence: 99%

See 1 more Smart Citation

Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouse

et al. 2014

Self Cite

View full text Add to dashboard Cite

Rationale Methylone, a new drug of abuse sold as "bath salts" has similar effects to ecstasy or cocaine.Objective We have investigated changes in dopaminergic and serotoninergic markers, indicative of neuronal damage, induced by methylone in the frontal cortex, hippocampus and striatum of mice and according two different treatment schedules. Conclusions The neural effects of methylone differ depending upon the treatment schedule. Neurochemical changes elicited by methylone are apparent when administered at an elevated ambient temperature, four times per day at 3 h intervals, which is in accordance with its short half-life. Methods

show abstract

Section: Page 14 Of 29 Psychopharmacologysupporting

confidence: 86%

Section: Depressant-like Effect Of Methylonementioning

confidence: 99%

Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouse

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…By contrast, Lopez-Arnau et al (2013) found no evidence for non-linear PKs in rats after oral Figure 5 Dose-response effects of methylone, MDC, HHMC, and HMMC on extracellular dopamine (DA) in male rats undergoing in vivo microdialysis in nucleus accumbens. Drug-treated rats received iv injections of 1 mg/kg at time 0, followed by 3 mg/kg 60 min later.…”

Section: Discussionmentioning

confidence: 99%

“…Methylone is a popular drug of abuse, yet few studies have addressed its PK and metabolism in animal models (Kamata et al, 2006;Lopez-Arnau et al, 2013). Here we examined the plasma PK profiles and pharmacodynamic effects for methylone and its phase I metabolites in conscious rats.…”

Section: Discussionmentioning

confidence: 99%

“…Methylone is primarily biotransformed by cytochrome p450 2D6 (CYP2D6) in humans, the same isoform responsible for metabolism of MDMA (Pedersen et al, 2013). Lopez-Arnau et al (2013) evaluated methylone PK and pharmacodynamic effects in rats and found that methylone exhibits rapid kinetics, with peak blood concentrations occurring 30 min after oral administration, and readily crosses the blood-brain barrier (Lopez-Arnau et al, 2013). In the study of Lopez-Arnau et al (2013), methylone concentrations in plasma correlated with locomotor activation, although the authors speculated that metabolites may also be bioactive.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Elmore

Dillon‐Carter

Partilla

et al. 2016

Neuropsychopharmacol

View full text Add to dashboard Cite

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.

show abstract

Identification of polymorphism in ethylone hydrochloride: synthesis and characterization

Maheux

Alarcon

Copeland

et al. 2015

Drug Testing and Analysis

View full text Add to dashboard Cite

Ethylone, a synthetic cathinone with psychoactive properties, is a designer drug which has appeared on the recreational drug market in recent years. Since 2012, illicit shipments of ethylone hydrochloride have been intercepted with increasing frequency at the Canadian border. Analysis has revealed that ethylone hydrochloride exists as two distinct polymorphs. In addition, several minor impurities were detected in some seized exhibits. In this study, the two conformational polymorphs of ethylone hydrochloride have been synthesized and fully characterized by FTIR, FT‐Raman, powder XRD, GC‐MS, ESI‐MS/MS and NMR (13C CPMAS, 1H, 13C). The two polymorphs can be distinguished by vibrational spectroscopy, solid‐state nuclear magnetic resonance spectroscopy and X‐ray diffraction. The FTIR data are applied to the identification of both polymorphs of ethylone hydrochloride (mixed with methylone hydrochloride) in a laboratory submission labelled as 'Ocean Snow Ultra’. The data presented in this study will assist forensic scientists in the differentiation of the two ethylone hydrochloride polymorphs. This report, alongside our recent article on the single crystal X‐ray structure of a second polymorph of this synthetic cathinone, is the first to confirm polymorphism in ethylone hydrochloride. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd.

show abstract

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

Cited by 50 publications

References 37 publications

Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouse

Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouse

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

Identification of polymorphism in ethylone hydrochloride: synthesis and characterization

Contact Info

Product

Resources

About