methylone and cathinone

methylone has been researched along with cathinone* in 29 studies

Reviews

5 review(s) available for methylone and cathinone

ArticleYear
A review of the influence of functional group modifications to the core scaffold of synthetic cathinones on drug pharmacokinetics.
    Psychopharmacology, 2019, Volume: 236, Issue:3

    The synthetic cathinones are a class of designer drugs of abuse that share a common core scaffold. The pharmacokinetic profiles of the synthetic cathinones vary based on the substitutions to the core scaffold.. To provide a summary of the literature regarding the pharmacokinetic characteristics of the synthetic cathinones, with a focus on the impact of the structural modifications to the pharmacokinetics.. In many, but not all, instances the pharmacokinetic characteristics of the synthetic cathinones can be reasonably predicted based on the substitutions to the core scaffold. Mephedrone and methylone are chemically alike and have similar T. Continued research will lead to a better understanding of the pharmacokinetic changes associated with structural modifications to the cathinone scaffold, and potentially in the long range, enhanced overdose and addiction therapy. Additionally, the areas of polydrug use and pharmacogenetics have been largely overlooked with regard to synthetic cathinones.

    Topics: Alkaloids; Amphetamines; Animals; Designer Drugs; Humans; Methamphetamine; Substance-Related Disorders; Synthetic Drugs

2019
Synthetic cathinones related fatalities: an update.
    European review for medical and pharmacological sciences, 2018, Volume: 22, Issue:1

    Synthetic cathinones, more commonly known as "bath salts", are synthetic drugs chemically related to cathinone, a psychostimulant found in the khat plant. They are the first most consumed products among new psychoactive substances, which cause psychostimulant and hallucinogenic effects determining a number of fatalities worldwide.  In this paper, we have systematically reviewed cases of synthetic cathinones-related fatalities analytically confirmed, which have occurred in the last few years.. Relevant scientific articles were identified in Medline, Cochrane Central, Scopus, Web of Science and Institutional/government websites up to November 2017 using the following keywords: synthetic cathinones, mephedrone, methylenedioxypyrovalerone, MDPV, methylone, ethylone, buthylone, fatal intoxication, fatalities and death.. In total, 20 citations met the criteria for inclusion, representing several fatal cases with analytically confirmed synthetic cathinones in biological sample/s of the deceased. The death was attributed to hyperthermia, hypertension, cardiac arrest and more in general to the classic serotonin syndrome. Only rarely did the concentration of the parent drug causing fatality overcome the value of 1 mg/L in post-mortem biological fluids.. Abuse of synthetic cathinones still represents a serious public health issue. Systematic clinical studies on both the animal and human model are lacking; therefore, the only available data are from the users who experience the possible hazardous consequences. Analytical methodologies for the identification of parent compounds and eventual metabolites both in ante-mortem and post-mortem cases need to be developed and validated. Analytical data should be shared through different communication platforms with the aim of stopping this serious health threat for drug users.

    Topics: Alkaloids; Autopsy; Central Nervous System Stimulants; Death; Fever; Heart Arrest; Humans; Methamphetamine; Substance-Related Disorders

2018
DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants.
    ACS chemical neuroscience, 2018, 10-17, Volume: 9, Issue:10

    Cathinone is a plant alkaloid found in khat leaves of perennial shrubs grown in East Africa. Similar to cocaine, cathinone elicits psychostimulant effects which are in part attributed to its amphetamine-like structure. Around 2010, home laboratories began altering the parent structure of cathinone to synthesize derivatives with mechanisms of action, potencies, and pharmacokinetics permitting high abuse potential and toxicity. These "synthetic cathinones" include 4-methylmethcathinone (mephedrone), 3,4-methylenedioxypyrovalerone (MDPV), and the empathogenic agent 3,4-methylenedioxymethcathinone (methylone) which collectively gained international popularity following aggressive online marketing as well as availability in various retail outlets. Case reports made clear the health risks associated with these agents and, in 2012, the Drug Enforcement Agency of the United States placed a series of synthetic cathinones on Schedule I under emergency order. Mechanistically, cathinone and synthetic derivatives work by augmenting monoamine transmission through release facilitation and/or presynaptic transport inhibition. Animal studies confirm the rewarding and reinforcing properties of synthetic cathinones by utilizing self-administration, place conditioning, and intracranial self-stimulation assays and additionally show persistent neuropathological features which demonstrate a clear need to better understand this class of drugs. This Review will thus detail (i) historical context of cathinone use and the rise of "dark" synthetic derivatives, (ii) structural features and mechanisms of synthetic cathinones, (iii) behavioral effects observed clinically and in animals under controlled laboratory conditions, and (iv) neurotransmitters and circuits that may be targeted to manage synthetic cathinone abuse in humans.

    Topics: Alkaloids; Animals; Behavior, Animal; Benzodioxoles; Body Temperature; Catha; Central Nervous System Stimulants; Dopamine; History, 21st Century; History, Medieval; Humans; Locomotion; Methamphetamine; Pyrrolidines; Serotonin; Substance-Related Disorders; Synaptic Transmission; Synthetic Cathinone

2018
Behavioral pharmacology of designer cathinones: a review of the preclinical literature.
    Life sciences, 2014, Feb-27, Volume: 97, Issue:1

    "Bath salts" is one street name for a family of synthetic cathinones that display pharmacological effects resembling cocaine and commonly abused amphetamines. Despite extensive legislation aimed at the criminalization of bath salts, several designer cathinones are gaining a foothold in the illicit drug scene; for example, in the United Kingdom, mephedrone (4-methylmethcathinone, MEPH) is highly popular among drug abusers whereas, in the United States, MDPV (methylenedioxypyrovalerone) and methylone are highly prevalent. To date, knowledge about the hazards of designer cathinones is based mostly on hospital reports and anecdotal evidence derived from online surveys. Despite the paucity of preclinical studies directed toward designer cathinones, a number of invaluable findings arising from those studies are enabling scientists to develop their neuropharmacological profiles. Despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce different behavioral effects, including unique effects on locomotor activity, learning, anxiety, thermoregulation, and abuse liability. The present review will discuss the behavioral effects of MEPH, MDPV, and methylone and compare those effects to established psychostimulant drugs. The rise in the use of designer cathinones in the United States and abroad justifies further investigations into these compounds, both for a greater understanding of the danger that "bath salts" pose to the public, and to provide insight into replacement cathinones as they emerge onto the market.

    Topics: Alkaloids; Animals; Benzodioxoles; Central Nervous System Stimulants; Designer Drugs; Drug Evaluation, Preclinical; Humans; Illicit Drugs; Methamphetamine; Pyrrolidines; Substance-Related Disorders; Synthetic Cathinone

2014
GHB and synthetic cathinones: clinical effects and potential consequences.
    Drug testing and analysis, 2011, Volume: 3, Issue:9

    Designer drugs belong to a group of legally or illegally produced substances that are structurally and pharmacologically very similar to illicit drugs. In the past, designer drugs were often used during all-night dance parties, but they are now consumed in multiple settings from college bars to parks to private house parties. Most of these club drugs can be bought on legal websites and home-delivered for private parties. Recently, legal highs have once again become a burning media issue across the world. Our review will focus on GHB and synthetic cathinones. Literature searches were conducted for the period from 1975 to July 2010 using PubMed, EMBASE, PsycInfo, Internet underground and governmental websites using the following keywords alone or in combination: designer drugs, club drugs, party drugs, GHB, synthetic cathinones, mephedrone, methylone, flephedrone, MDAI, and MDVP. Available epidemiological, neurobiological, and clinical data for each compound are described. There is evidence that negative health and social consequences may occur in recreational and chronic users. The addictive potential of designer drugs is not weak. Non-fatal overdoses and deaths related to GHB/GBL or synthetic cathinones have been reported. Clinicians must be careful with GBL or synthetic cathinones, which are being sold and used as substitutes for GHB and MDMA, respectively. Interventions for drug prevention and harm reduction in response to the use of these drugs should be implemented on the Internet and in recreational settings. Prevention, Information, Action, and Treatment are the main goals that must be addressed for this new potentially addictive problem.

    Topics: Alkaloids; Animals; Designer Drugs; Humans; Illicit Drugs; Indans; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Sodium Oxybate; Substance-Related Disorders

2011

Other Studies

24 other study(ies) available for methylone and cathinone

ArticleYear
Reinforcing effects of synthetic cathinones in rhesus monkeys: Dose-response and behavioral economic analyses.
    Pharmacology, biochemistry, and behavior, 2021, Volume: 202

    The abuse of synthetic cathinones ("bath salts") with psychomotor stimulant and/or entactogenic properties emerged as a public health concern when they were introduced as "legal" alternatives to drugs of abuse such as cocaine or MDMA. In this study, experiments were conducted in nonhuman primates to examine how differences in transporter selectivity might impact the reinforcing effects of synthetic cathinones. Rhesus monkeys (N = 5) were trained to respond for intravenous injections under a fixed-ratio (FR) 30, timeout 60-s schedule of reinforcement. The reinforcing effects of selected cathinones (e.g., MDPV, αPVP, MCAT, and methylone) with a range of pharmacological effects at dopamine and serotonin transporters were compared to cocaine and MDMA using dose-response analysis under a simple FR schedule and behavioral economic procedures that generated demand curves for two doses of each drug. Results show that one or more doses of all drugs were readily self-administered in each subject and, excepting MDMA (21 injections/session), peak levels of self-administration were similar across drugs (between 30 and 40 injections/session). Demand elasticity for the peak and the peak + 1/2-log dose of each drug did not significantly differ, and when data for the two doses were averaged for each drug, the following rank-order of reinforcing strength emerged: cocaine > MCAT = MDPV = methylone > αPVP = MDMA. These results indicate that the reinforcing strength of synthetic cathinones are not related to their selectivity in binding dopamine or serotonin transporter sites.

    Topics: Alkaloids; Animals; Behavior, Animal; Benzodioxoles; Central Nervous System Stimulants; Cocaine; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; Female; Macaca mulatta; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Pentanones; Protein Binding; Pyrrolidines; Reinforcement, Psychology; Self Administration; Serotonin Plasma Membrane Transport Proteins; Synthetic Cathinone; Synthetic Drugs

2021
S-(+)-Pentedrone and R-(+)-methylone as the most oxidative and cytotoxic enantiomers to dopaminergic SH-SY5Y cells: Role of MRP1 and P-gp in cathinones enantioselectivity.
    Toxicology and applied pharmacology, 2021, 04-01, Volume: 416

    Cathinone derivatives are the most representative group within new drugs market, which have been described as neurotoxic. Since cathinones, as pentedrone and methylone, are available as racemates, it is our aim to study the neuronal cytotoxicity induced by each enantiomer. Therefore, a dopaminergic SH-SY5Y cell line was used to evaluate the hypothesis of enantioselectivity of pentedrone and methylone enantiomers on cytotoxicity, oxidative stress, and membrane efflux transport (confirmed by in silico studies). Our study demonstrated enantioselectivity of these cathinones, being the S-(+)-pentedrone and R-(+)-methylone the most oxidative enantiomers and also the most cytotoxic, suggesting the oxidative stress as main cytotoxic mechanism, as previously described in in vitro studies. Additionally, the efflux transporter multidrug resistance associated protein 1 (MRP1) seems to play, together with GSH, a selective protective role against the cytotoxicity induced by R-(-)-pentedrone enantiomer. It was also observed an enantioselectivity in the binding to P-glycoprotein (P-gp), another efflux protein, being the R-(-)-pentedrone and S-(-)-methylone the most transported enantiomeric compounds. These results were confirmed, in silico, by docking studies, revealing that R-(-)-pentedrone is the enantiomer with highest affinity to MRP1 and S-(-)-methylone and R-(-)-pentedrone are the enantiomers with highest affinity to P-gp. In conclusion, our data demonstrated that pentedrone and methylone present enantioselectivity in their cytotoxicity, which seems to involve different oxidative reactivity as well as different affinity to the P-gp and MRP1 that together with GSH play a protective role.

    Topics: Alkaloids; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Cell Survival; Dopaminergic Neurons; Dose-Response Relationship, Drug; Glutathione; Humans; Methamphetamine; Methylamines; Molecular Docking Simulation; Multidrug Resistance-Associated Proteins; Oxidative Stress; Pentanones; Protein Binding; Stereoisomerism

2021
Discriminative-Stimulus Effects of Synthetic Cathinones in Squirrel Monkeys.
    The international journal of neuropsychopharmacology, 2021, 08-20, Volume: 24, Issue:8

    Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine [MDMA])-presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not been fully examined in nonhuman primates.. The present studies were conducted to systematically evaluate the discriminative stimulus effects of 5 abused synthetic cathinones (methylenedioxypyrovalerone [MDPV], α-pyrrolidinovalerophenone [α-PVP], methcathinone [MCAT], mephedrone, and methylone) in adult male squirrel monkeys trained to distinguish intramuscular injections of MA (0.1 mg/kg; n = 4) or MDMA (0.6 mg/kg; n = 4) from vehicle.. Each training drug produced dose-dependent effects and, at the highest dose, full substitution. MDMA produced predominantly vehicle-like responding in the MA-trained group, whereas the highest dose of MA (0.56 mg/kg) produced partial substitution (approximately 90% appropriate lever responding in one-half of the subjects) in the MDMA-trained group. MDPV, α-PVP, and MCAT produced full substitution in MA-trained subjects, but, at the same or higher doses, only substituted for MDMA in one-half of the subjects, consistent with primarily dopaminergically mediated interoceptive effects. In contrast, mephedrone and methylone fully substituted in MDMA-trained subjects but failed to fully substitute for the training drug in MA-trained subjects, suggesting a primary role for serotonergic actions in their interoceptive effects.. These findings suggest that differences in the interoceptive effects of synthetic cathinones in nonhuman primates reflect differing compositions of monoaminergic actions that also may mediate their subjective effects in humans.

    Topics: Alkaloids; Animals; Behavior, Animal; Benzodioxoles; Central Nervous System Stimulants; Discrimination Learning; Interoception; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Propiophenones; Psychotropic Drugs; Pyrrolidines; Saimiri; Synthetic Cathinone

2021
Pharmacokinetics of Synthetic Cathinones Found in Bath Salts in Mouse Brain and Plasma Using High-Pressure Liquid Chromatography-Tandem Mass Spectrometry.
    European journal of drug metabolism and pharmacokinetics, 2021, Volume: 46, Issue:6

    Approximately 10 years ago, "bath salts" became popular as legal alternatives to the psychostimulants cocaine and the amphetamines. These products contained synthetic cathinones, including 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxymethcathinone (methylone). Most preclinical investigations have only assessed the effects of these synthetic cathinones independently; however, case reports and Drug Enforcement Administration (DEA) studies indicate that bath salts contain mixtures of these substances. In this study, we examine the pharmacokinetic interactions of the drug combination. We hypothesized that combined exposure to MDPV, mephedrone, and methylone would result in increased drug concentrations and enhanced total drug concentrations when compared to individual administration.. Adolescent male Swiss-Webster mice were injected intraperitoneally with either 10 mg/kg MDPV, 10 mg/kg mephedrone, 10 mg/kg methylone, or 10 mg/kg combined MDPV, mephedrone, and methylone. Following injection, brains and plasma were collected at 1, 10, 15, 30, 60, and 120 min. Drugs were extracted via solid-phase extraction, and concentrations were determined using a previously published high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.. All drugs crossed the blood-brain barrier quickly. For methylone, the maximal concentration (C. The pharmacokinetics of methylone, mepedrone, and MDPV are altered when the drugs are used in combination. These data provide insight into the consequences of co-exposure to synthetic cathinones in popular bath salt products.

    Topics: Alkaloids; Animals; Benzodioxoles; Blood-Testis Barrier; Brain; Central Nervous System Stimulants; Chromatography, High Pressure Liquid; Male; Methamphetamine; Mice; Pyrrolidines; Salts; Synthetic Cathinone; Tandem Mass Spectrometry

2021
Determination of New Psychoactive Substances in Whole Blood Using Microwave Fast Derivatization and Gas Chromatography/Mass Spectrometry.
    Journal of analytical toxicology, 2020, Jan-07, Volume: 44, Issue:1

    The production and consumption of new psychoactive substances (NPSs) has been raising a major concern worldwide. Due to easy access and available information, many NPSs continue to be synthesized with an alarming increase of those available to purchase, despite all the control efforts created. A new analytical method was developed and validated to determine a group of phenethylamines and synthetic cathinones: cathinone, flephedrone, buphedrone, 4-MTA, α-PVP, methylone, 2C-P, ethylone, pentylone, MDPV and bromo-dragonFLY in whole blood. A mixed-mode solid phase extraction was applied to 250 μL of sample, and the extracts were derivatized with fast microwave technique before being analyzed by gas chromatography-mass spectrometry (GC-MS). The validation procedure followed the Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines with parameters that included selectivity, linearity, limits of detection and quantification, intra- and inter-day precision and accuracy, recoveries and stability. The method presented linearity between 5 and 500 ng/mL for cathinone, buphedrone, 4-MTA, methylone, 2C-P and bromo-dragonFLY, 10-500 ng/mL for flephedrone, ethylone, pentylone and MDPV, and 40-500 ng/mL for α-PVP, with determination coefficients above 0.99 for all analytes. Recoveries ranged between 70.3% and 116.6%, and regarding intra- and inter-day precision, the relative mean errors were typically lower than 8.6%. The method was successfully applied to over 100 authentic samples from the Laboratory of Chemistry and Forensic Toxicology, Centre Branch, of the National Institute of Legal Medicine and Forensic Sciences, Portugal.

    Topics: Acetone; Alkaloids; Amphetamines; Designer Drugs; Ethylamines; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Limit of Detection; Methamphetamine; Microwaves; Pentanones; Phenethylamines; Psychotropic Drugs; Pyrrolidines; Substance Abuse Detection

2020
Synthetic cathinones and their phenethylamine analogues produce distinct psychomotor and reward behavior in crayfish.
    Behavioural brain research, 2020, 02-03, Volume: 379

    Synthetic cathinones share potent sympathomimetic properties with amphetamines due to their shared phenethylamine backbone. Despite recent work focused on understanding the behavioral effects of synthetic cathinones, a systematic comparison of neuropharmacology, behavior, and physiological effects with other stimulants, has remained elusive. In the present study, we explore the behavioral effects of cathinones in crayfish, a model system which combines a well characterized behavioral paradigm for addiction-like behaviors, a modularly organized nervous system, the lack of a formal blood-brain barrier, and experimental tractability. The objective of this study was to characterize the psychomotor and rewarding effects of methylated cathinones (methylone, mephedrone), and their non β-ketone substituted amphetamine analogs (4-methylmethamphetamine, 4-MMA and 3,4-methylenedioxymethamphetamine MDMA) in crayfish. Our results suggest that these drugs produce psychostimulation, which sensitizes upon repeated drug administration. Furthermore, crayfish demonstrated a conditioned substrate preference for mephedrone and 4-MMA drug-pairings at a 10 μg/g dose, a preference which persisted even through a series of extinction trials. Our study indicates that synthetic cathinones and substituted amphetamine analogues produce distinct behavioral effects in an invertebrate system which consists of a relatively simple neuronal organization. The present findings provide an evolutionary context to our understanding about how drugs of abuse initiate reward at levels far beyond those specific to humans.

    Topics: Alkaloids; Amphetamines; Animals; Astacoidea; Behavior, Animal; Central Nervous System Sensitization; Central Nervous System Stimulants; Conditioning, Psychological; Male; Methamphetamine; Motor Activity; N-Methyl-3,4-methylenedioxyamphetamine; Phenethylamines; Reward

2020
Enantioselectivity on the absorption of methylone and pentedrone using Caco-2 cell line: Development and validation of an UHPLC method for cathinones quantification.
    Toxicology and applied pharmacology, 2020, 05-15, Volume: 395

    Synthetic cathinones, such as methylone and pentedrone, are psychoactive derivatives of cathinone, sold in the internet as "plant food" or "bath salts". However, the level at which these compounds and their enantiomers cross the intestinal barrier has not been yet determined. Thus, the present study aimed to analyze the enantioselectivity on the permeability of these drugs through the intestinal barrier by using the Caco-2 cell line, a widely used in vitro model for drug permeability studies. To achieve this goal, an UHPLC-UV method was developed and validated to quantify both synthetic cathinones. The developed UHPLC-UV method revealed high selectivity and a linearity from 1 to 500 μM with correlation coefficients always higher than 0.999. The method has an accuracy that ranged between 89 and 107%, inter-day and intra-day precisions with coefficients of variation below 10%, limits of detection and quantification of 0.31 μM and 0.93 μM for methylone and 0.17 μM and 0.52 μM for pentedrone, respectively. In Caco-2 cells, a differentiated passage of the enantiomers across monolayer was observed for both cathinones. For pentedrone, the difference was observed after the first hour, being R-(-)-pentedrone the most permeable compound. Regarding methylone, the difference was noted after one hour and 30 min, with S-(-)-methylone being the most absorbed enantiomer. In conclusion, a fully validated method was successfully applied for studying the permeability of methylone and pentedrone enantiomers in an in vitro model of human intestine, which allowed to discover, for the first time, the enantioselectivity in drug permeability of this class of drugs.

    Topics: Alkaloids; Caco-2 Cells; Chromatography, High Pressure Liquid; Humans; Intestinal Absorption; Methamphetamine; Methylamines; Pentanones; Permeability; Psychotropic Drugs; Sensitivity and Specificity; Stereoisomerism; Structure-Activity Relationship

2020
The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells.
    Toxicology letters, 2020, Oct-01, Volume: 331

    Synthetic cathinones abuse remains a serious public health problem. Kidney injury has been reported in intoxications associated with synthetic cathinones, but the molecular mechanisms involved have not been explored yet. In this study, the potential in vitro nephrotoxic effects of four commonly abused cathinone derivatives, namely pentedrone, 3,4-dimethylmethcatinone (3,4-DMMC), methylone and 3,4-methylenedioxypyrovalerone (MDPV), were assessed in the human kidney HK-2 cell line. All four derivatives elicited cell death in a concentration- and time-dependent manner, in the following order of potency: 3,4-DMMC >> MDPV > methylone ≈ pentedrone. 3,4-DMMC and methylone were selected to further elucidate the mechanisms behind synthetic cathinones-induced cell death. Both drugs elicited apoptotic cell death and prompted the formation of acidic vesicular organelles and autophagosomes in HK-2 cells. Moreover, the autophagy inhibitor 3-methyladenine significantly potentiated cell death, indicating that autophagy may serve as a cell survival mechanism that protects renal cells against synthetic cathinones toxicity. Both drugs triggered a rise in reactive oxygen and nitrogen species formation, which was completely prevented by antioxidant treatment with N‑acetyl‑L‑cysteine or ascorbic acid. Importantly, these antioxidant agents significantly aggravated renal cell death induced by cathinone derivatives, most likely due to their autophagy-blocking properties. Taken together, our results support an intricate control of cell survival/death modulated by oxidative stress, apoptosis and autophagy in synthetic cathinones-induced renal injury.

    Topics: Alkaloids; Apoptosis; Autophagy; Benzodioxoles; Cell Culture Techniques; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Humans; Illicit Drugs; Kidney; Methamphetamine; Methylamines; Pentanones; Pyrrolidines; Reactive Nitrogen Species; Reactive Oxygen Species; Synthetic Cathinone; Time Factors

2020
The synthetic cathinones, butylone and pentylone, are stimulants that act as dopamine transporter blockers but 5-HT transporter substrates.
    Psychopharmacology, 2019, Volume: 236, Issue:3

    Synthetic cathinones continue to emerge in recreational drug markets worldwide. 1-(1,3-Benzodioxol-5-yl)-2-(methylamino)butan-1-one (butylone) and 1-(1,3-benzodioxol-5-yl)-2-(methylamino)pentan-1-one (pentylone) are derivatives of the cathinone compound, 1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one (methylone), that are being detected in drug products and human casework.. The purpose of the present study was to examine the neuropharmacology of butylone and pentylone using in vitro and in vivo methods.. In vitro uptake and release assays were carried out in rat brain synaptosomes and in cells expressing human dopamine transporters (DAT) and 5-HT transporters (SERT). In vivo microdialysis was performed in the nucleus accumbens of conscious rats to assess drug-induced changes in neurochemistry.. Our data demonstrate that increasing the α-carbon chain length of methylone creates "hybrid" transporter compounds which act as DAT blockers but SERT substrates. Nevertheless, butylone and pentylone elevate extracellular dopamine and stimulate motor activity, suggesting both drugs possess significant risk for abuse.

    Topics: 3,4-Methylenedioxyamphetamine; Alkaloids; Amphetamines; Animals; Central Nervous System Stimulants; Dopamine Antagonists; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Male; Methamphetamine; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Synaptosomes; Synthetic Drugs

2019
Cytotoxicity of new psychoactive substances and other drugs of abuse studied in human HepG2 cells using an adopted high content screening assay.
    Toxicology letters, 2019, Volume: 301

    New psychoactive substances (NPS) are still an emerging issue in clinical and forensic toxicology. Information about their cytotoxic potential is limited or even unavailable before distribution and thus their intake can be of high risk for consumers. The aim of the presented study was to develop a strategy to identify cytotoxic potential of NPS based on a high content screening assay (HCSA) using HepG2 cell line and four fluorescent dyes, namely Hoechst33342, TMRM, CAL-520, and TOTO-3. The HCSA was optimized to work without an automated analyzer by using the model compounds fluvastatin, paracetamol, propranolol, and simvastatin. The following parameters were monitored: stained nuclei as a measure for cell count as well as nuclear size and nuclear intensity (all Hoechst33342), mitochondrial membrane potential (TMRM), cytosolic calcium level (CAL-520), and plasma membrane integrity (TOTO-3). The present study showed strong cytotoxic potential for the NPS 5F-PB-22 and MDAI, moderate effects for MDMA, MDPV, methylone, cathinone, 4-MEC, and mephedrone, and no toxic effects for methamphetamine. To assess the metabolic suitability of HepG2 cells under the chosen conditions, cell culture supernatants were analyzed by liquid chromatography-high resolution-tandem mass spectrometry. Metabolites were merely detected for lipophilic drugs such as 5F-PB-22 and MDPV and in addition with a much lower abundance in comparison to the parent compound but the study only allowed a qualitative look for metabolites and the used liver cell line might not ideal when considering metabolism.

    Topics: Acetaminophen; Alkaloids; Biological Assay; Chromatography, Liquid; Fluorescent Dyes; Fluvastatin; Hep G2 Cells; Hepatocytes; Humans; Illicit Drugs; Indans; Indoles; Membrane Potential, Mitochondrial; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Propranolol; Quinolines; Simvastatin; Tandem Mass Spectrometry; Toxicity Tests

2019
Synthetic cathinones in Southern Germany - characteristics of users, substance-patterns, co-ingestions, and complications.
    Clinical toxicology (Philadelphia, Pa.), 2017, Volume: 55, Issue:6

    To define the characteristics of synthetic cathinone users admitted to hospital including clinical and laboratory parameters and the complications of use.. Retrospective single-center study of patients treated for acute cathinone intoxication and complications of cathinone use between January 2010 and January 2016.. A specialized clinical toxicology unit at an academic tertiary care center in Southern Germany serving a population of about 4 million.. 81 consecutive patients with laboratory-confirmed use of cathinones who presented for acute intoxication or complications of cathinone use were retrospectively analyzed.. The patients were predominantly male (64%, 52/81) with a median age of 34 years. 60 were admitted for signs of acute intoxication while 21 suffered from complications of cathinone use. 70% of acutely intoxicated patients had an increased creatinine phosphokinase. Only a minority of patients presented with a sympathomimetic toxidrome. Three patients had infectious complications, 10 prolonged psychosis, 6 rhabdomyolyses and/or kidney failure, and two patients died. Based on presentations, cathinone use has increased with the first cases seen in 2010. Opiates/opioids are the main co-ingested drugs of abuse. The pattern of cathinone use shifted from methylone in 2010/2011 to 3,4-methylenedioxypyrovalerone (MDPV) and 3-methylmethcathinone (3-MMC) in 2014/2015. We conclude that in our setting "typical" cathinone users are males in their thirties. They are seldom drug naïve and regularly co-ingest illicit drugs. Preventive measures have to be tailored to these difficult to reach patients. Present efforts to educate young clubbers in their late teens may fail to reach the pertinent demographic.

    Topics: Academic Medical Centers; Adolescent; Adult; Alkaloids; Benzodioxoles; Female; Germany; Hospitalization; Humans; Illicit Drugs; Male; Methamphetamine; Middle Aged; Pyrrolidines; Retrospective Studies; Substance-Related Disorders; Synthetic Cathinone; Young Adult

2017
The pharmacokinetic profile of synthetic cathinones in a pregnancy model.
    Neurotoxicology and teratology, 2017, Volume: 63

    In recent years, the abuse of synthetic cathinones or 'bath salts' has become a major public health concern. Although these compounds were initially sold legally and labeled "not for human consumption", the 'bath salts' are psychostimulants, with similar structures and pharmacologic mechanisms to cocaine, the amphetamines, and 3,4 methylendioxymethamphetamine (MDMA, Molly, or Ecstasy). The reported use of these substances by women of child-bearing age highlights the necessity of studies seeking to delineate risks of prenatal exposure. Three popular drugs of this type are methylone, mephedrone, and 3, 4-methylenedioxypyrovalerone (MDPV). Unfortunately, there is currently no information available on the teratogenicity of these compounds, or of the extent to which they cross the placenta. As such, the purpose of this study was to examine the pharmacokinetic profile of the 'bath salts' in a pregnancy model. Pregnant mice (E17.5 gestation) were injected intraperitoneally with a cocktail of 5mg/kg methylone, 10mg/kg mephedrone, and 3mg/kg (MDPV) dissolved in sterile saline. Maternal brain, maternal plasma, placenta, and fetal brain were collected at 30s, 1min, 5min, 10min, 15min, 30min, 1h, 2h, 4h, and 8h following injection. Methylone, mephedrone, and MDPV were extracted from tissue by solid phase extraction, and concentrations were determined using a previously validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Interestingly, all 3 cathinones reached measurable concentrations in the placenta, as well as the fetal brain; in fact, for MDPV, the maximal concentration (Cmax) was highest in fetal brain, while mephedrone's highest Cmax value was achieved in placenta. Additionally, the total drug exposure for all 3 compounds (as represented by area under the curve, AUC) was higher in fetal matrices (placenta and fetal brain) than in maternal matrices (maternal brain and plasma), and the half-lives for the drugs were longer. Given the extensive presence of methylone, mephedrone, and MDPV in the fetal brain following prenatal exposure, fetal risk is definitely a concern. As there are currently no prenatal studies available on the teratogenicity of these agents, pregnant patients should be informed about the potential risks that these substances may have.

    Topics: Alkaloids; Animals; Brain; Central Nervous System Stimulants; Female; Methamphetamine; Mice; Pregnancy; Pyrrolidines

2017
A Validated Method for the Detection of 32 Bath Salts in Oral Fluid.
    Journal of analytical toxicology, 2017, Oct-01, Volume: 41, Issue:8

    Workplace drug testing in Australia is usually adherent to one of two standards, AS/NZS 4308:2008 for urine or AS 4760:2006 for oral fluid. These standards prescribe the drugs tested, devices used and testing methodology followed by the testing agency. However, they are not comprehensive and for many years workers have been able to consume novel psychoactive substances to avoid detection and without consequences. Here, we present a validated method for the detection of 32 Synthetic Stimulant and Hallucogenic drugs, commonly sold as bath salts, in oral fluid. These drugs are cathinone, ephedrone, methylone, flephedrone, MDA, PMA, methedrone, TMA, MDMA, butylone, mephedrone, MDEA, MEC, pentedrone, MBDB, MTA, Alpha-PVP, MPBP, 2C-B, MDPV, DOB, 2C-T-2, TFMPP, DOET, 2C-T-7, naphyrone, MDAI, FMA, DMA, 25C-NBOMe, 25B-NBOMe and 25T4-NBOMe. Sample preparation was undertaken using a simple protein precipitation in acetonitrile. Chromatographic separation was achieved in 7.5 min on a Kinetex F5 column (50 mm × 3 mm × 2.6 μm) using 0.1% formic acid in water and acetonitrile as the mobile phases. The method was validated with limit of detection (1 ng/mL), limit of quantitation (2.5 ng/mL), selectivity, linearity (2.5-500 ng/mL), accuracy (85.3-108.4% of the target concentration) and precision (1.9-14%). This method was applied to 12 samples previously submitted for routine testing and two were found to contain 2-CB and DOB (5 and 4 ng/mL) and, MPBP and TFMPP (both at 4 ng/mL). This method provides for the rapid detection of a large number of compounds in oral fluid which is readily applicable to routine testing laboratories.

    Topics: Alkaloids; Anisoles; Australia; Benzylamines; Dimethoxyphenylethylamine; Humans; Illicit Drugs; Methamphetamine; Pentanones; Phenethylamines; Propiophenones; Psychotropic Drugs; Pyrrolidines; Saliva; Substance Abuse Detection

2017
Solid-phase extraction followed by liquid chromatography-high resolution mass spectrometry to determine synthetic cathinones in different types of environmental water samples.
    Journal of chromatography. A, 2017, Nov-17, Volume: 1524

    Synthetic cathinones have become popular in recent years, which would explain why their determination in influent sewage samples has already been documented. In the present study a method based on solid-phase extraction followed by liquid chromatography and high resolution mass spectrometry is developed, validated and applied to determine twelve cathinones and one of their metabolites in different environmental samples including influent and effluent sewage and river water. Two cation-exchange sorbents (Oasis MCX and Oasis WCX) were compared, with better results achieved with Oasis WCX in terms of apparent recoveries (70-100%) and matrix effects (lower than -34%). The method was validated with effluent sewage samples providing suitable figures of merit, with method quantification limits ranging from 1ng/L to 5ng/L and method detection limits from 0.1ng/L to 0.5ng/L for all the compounds. Of the different cathinones studied, three, namely methylone, mephedrone metabolite and methylenedioxypyrovalerone, were quantified at concentration levels of low ng/L in each of the different samples analysed, while a number of the other cathinones were also detected in some of the samples.

    Topics: Alkaloids; Chromatography, Liquid; Environmental Monitoring; Fresh Water; Limit of Detection; Methamphetamine; Sewage; Solid Phase Extraction; Tandem Mass Spectrometry; Water Pollutants, Chemical

2017
Characteristics of the use of 3-MMC and other new psychoactive drugs in Slovenia, and the perceived problems experienced by users.
    The International journal on drug policy, 2016, Volume: 27

    The study presents the characteristics of the use of new psychoactive substances (NPS), the perceived problems experienced by users, and the reasons for cessation or cutting down. The research focused mainly on synthetic cathinones and the use of 3-MMC in Slovenia.. In order to research the characteristics of NPS use, we used a questionnaire which had been developed to determine the characteristics of the use of ATS and cocaine in the context of nightlife and was elaborated in our study on the use of mephedrone. The final non-representative sample included 249 users of NPS from Slovenia, who had completed an on-line survey over a period of 5 months in 2014. Part of the sampling was conducted on the ground and with the help of peer-groups. DrogArt's outreach workers and correspondents visited open public places, clubs, and discotheques to encourage users to participate in the survey.. Most users of NPS in Slovenia have tried NPS from the groups of synthetic cathinones and amphetamines. Most respondents included in the sample (67.9%) have tried 3-MMC, while 43.0% have tried methylone and 37.3% have tried mephedrone (4-MMC). Users attributed greater risks to the use of new drugs and preferred the effects of traditional drugs to those of new drugs. The most frequently reported problems were depression (55.2% of users), concentration difficulties (44.0%), damage to the mucous membrane of the nose and to the throat (39.8%), feelings of fear and anxiety (39.4%), and tingling in the arms or legs (34.4%). The main reasons for cutting down or discontinuing the use of NPS were 'fear of the health consequences', 'actual health consequences', and 'growing weary of using'. Among users of NPS, 7% have sought help, while 9.1% have considered doing so. The results also highlight differences between the NPS drug markets in Slovenia and the United Kingdom.. In 2014, the most frequently used NPS in Slovenia were synthetic cathinones such as 3-MMC. Users experienced various problems related to the use of NPS. However, they are familiar with recommendations on harm reduction and want additional information on the harmful effects of the use of NPS. Based on the obtained results, we can develop specific interventions in the area of harm reduction.

    Topics: Adolescent; Adult; Alkaloids; Amphetamine-Related Disorders; Female; Humans; Illicit Drugs; Male; Methamphetamine; Psychotropic Drugs; Slovenia; Surveys and Questionnaires; Young Adult

2016
Detection of "bath salts" and other novel psychoactive substances in hair samples of ecstasy/MDMA/"Molly" users.
    Drug and alcohol dependence, 2016, Apr-01, Volume: 161

    Ecstasy (MDMA) in the US is commonly adulterated with other drugs, but research has not focused on purity of ecstasy since the phenomenon of "Molly" (ecstasy marketed as pure MDMA) arose in the US.. We piloted a rapid electronic survey in 2015 to assess use of novel psychoactive substances (NPS) and other drugs among 679 nightclub/festival-attending young adults (age 18-25) in New York City. A quarter (26.1%) of the sample provided a hair sample to be analyzed for the presence of select synthetic cathinones ("bath salts") and some other NPS. Samples were analyzed using fully validated UHPLC-MS/MS methods. To examine consistency of self-report, analyses focused on the 48 participants with an analyzable hair sample who reported lifetime ecstasy/MDMA/Molly use.. Half (50.0%) of the hair samples contained MDMA, 47.9% contained butylone, and 10.4% contained methylone. Of those who reported no lifetime use of "bath salts", stimulant NPS, or unknown pills or powders, about four out of ten (41.2%) tested positive for butylone, methylone, alpha-PVP, 5/6-APB, or 4-FA. Racial minorities were more likely to test positive for butylone or test positive for NPS after reporting no lifetime use. Frequent nightclub/festival attendance was the strongest predictor of testing positive for MDMA, butylone, or methylone.. Results suggest that many ecstasy-using nightclub/festival attendees may be unintentionally using "bath salts" or other NPS. Prevention and harm reduction education is needed for this population and "drug checking" (e.g., pill testing) may be beneficial for those rejecting abstinence.

    Topics: Adolescent; Adult; Alkaloids; Animals; Drug Users; Female; Hair; Humans; Illicit Drugs; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; New York City; Self Report; Substance-Related Disorders; Surveys and Questionnaires; Tandem Mass Spectrometry; Young Adult

2016
Quantification of Synthetic Cathinones in Rat Brain Using HILIC-ESI-MS/MS.
    Journal of analytical toxicology, 2016, Volume: 40, Issue:9

    The abuse of synthetic cathinones, formerly marketed as "bath salts", has emerged over the last decade. Three common drugs in this class include 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxymethcathinone (methylone). An LC-MS/MS method has been developed and validated for the simultaneous quantification of MDPV, mephedrone, and methylone in brain tissue. Briefly, MDPV, mephedrone, methylone, and their deuterium-labeled analogs were subjected to solid phase extraction (SPE) and separated using an HILIC Silica Column. The HPLC was coupled to a Shimadzu IT-TOF (ion trap-time of flight) system with the electrospray source running in positive mode (+ESI). The method was validated for precision, accuracy, and extraction efficiency. All inter-day and intra-day % RSD (percent relative standard deviation) and % error values were less than 15% and extraction efficiency exceeded 80%. These conditions allowed for limits of detection of 1ng/mL for MDPV, and 5 ng/mL for both mephedrone and methylone. The limits of quantification were determined to be 5ng/mL for MDPV and 10 ng/mL for mephedrone and methylone. The method was utilized to evaluate the pharmacokinetics of these drugs in adult male rats following administration of a drug cocktail including MDPV, mephedrone, and methylone. All three compounds reached peak concentrations in the brain within 15 min. Although methylone and mephedrone were administered at the same dose, the peak concentration (C

    Topics: Alkaloids; Animals; Area Under Curve; Benzodioxoles; Brain; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Half-Life; Male; Methamphetamine; Pyrrolidines; Rats; Solid Phase Extraction; Spectrometry, Mass, Electrospray Ionization; Substance-Related Disorders; Synthetic Cathinone; Tandem Mass Spectrometry

2016
Ethylenedioxy homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and its corresponding cathinone analog methylenedioxymethcathinone: Interactions with transporters for serotonin, dopamine, and norepinephrine.
    Bioorganic & medicinal chemistry, 2015, Sep-01, Volume: 23, Issue:17

    N-Methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; 'Ecstasy'; 1) and its β-keto analog methylone (MDMC; 2) are popular drugs of abuse. Little is known about their ring-expanded ethylenedioxy homologs. Here, we prepared N-methyl-(3,4-ethylenedioxyphenyl)-2-aminopropane (EDMA; 3), both of its optical isomers, and β-keto EDMA (i.e., EDMC; 4) to examine their effects at transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET). In general, ring-expansion of the methylenedioxy group led to a several-fold reduction in potency at all three transporters. With respect to EDMA (3), S(+)3 was 6-fold, 50-fold, and 8-fold more potent than its R(-) enantiomer at SERT, DAT, and NET, respectively. Overall, in the absence of a β-carbonyl group, the ethylenedioxy (i.e., 1,4-dioxane) substituent seems better accommodated at SERT than at DAT and NET.

    Topics: Alkaloids; Dopamine; Dopamine Plasma Membrane Transport Proteins; Molecular Structure; N-Methyl-3,4-methylenedioxyamphetamine; Norepinephrine; Norepinephrine Plasma Membrane Transport Proteins; Serotonin; Serotonin Plasma Membrane Transport Proteins

2015
Crystallographic investigations of select cathinones: emerging illicit street drugs known as `bath salts'.
    Acta crystallographica. Section C, Structural chemistry, 2015, Volume: 71, Issue:Pt 1

    The name `bath salts', for an emerging class of synthetic cathinones, is derived from an attempt to evade prosecution and law enforcement. These are truly illicit drugs that have psychoactive CNS (central nervous system) stimulant effects and they have seen a rise in abuse as recreational drugs in the last few years since first having been seen in Japan in 2006. The ease of synthesis and modification of specific functional groups of the parent cathinone make these drugs particularly difficult to regulate. MDPV (3,4-methylenedioxypyrovalerone) is commonly encountered as its hydrochloride salt (C16H21NO3·HCl), in either the hydrated or the anhydrous forms. This `bath salt' has various names in the US, e.g. `Super Coke', `Cloud Nine', and `Ivory Wave', to name just a few. We report here the structures of two forms of the HCl salt, one as a mixed bromide/chloride salt, C16H22NO3(+)·0.343Br(-)·0.657Cl(-) [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one bromide/chloride (0.343/0.657)], and the other with the H7O3(+) cation, as well as the HCl counter-ion [systematic name: hydroxonium 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one dichloride, H7O3(+)·C16H22NO3(+)·2Cl(-)]. This is one of a very few structures (11 to be exact) in which we have a new example of a precisely determined hydroxonium cation. During the course of researching the clandestine manufacture of MDPV, we were surprised by the fact that a common precursor of this illicit stimulant is known to be the fragrant species piperonal, which is present in the fragrances of orchids, most particularly in the case of the vanilla orchid. We found that MDPV can be made by a Grignard reaction of this heliotropin. This may also explain the unexpected appearance of the bromide counter-ion in some of the salts we encountered (C16H21NO3·HBr), one of which is presented here [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one bromide, C16H22NO3(+)·Br(-)]. Complexation of MDPV with a forensic crystallizing reagent, HAuCl4, yields the tetrachloridoaurate salt of this drug, (C16H22NO3)[AuCl4]. The heavy-metal complexing agent HAuCl4 has been used for over a century to identify common quarternary nitrogen-containing drugs via microscopic identification. Another street drug, called ethylone (3,4-methylenedioxyethylcathinone), is regularly sold and abused as its hydrochloride salt (C12H15NO3·HCl), and its structure is herein described

    Topics: Alkaloids; Benzaldehydes; Benzodioxoles; Central Nervous System Stimulants; Crystallography, X-Ray; Designer Drugs; Drug Combinations; Humans; Illicit Drugs; Japan; Lidocaine; Methamphetamine; Psychotropic Drugs; Pyrrolidines; Salts; Substance-Related Disorders; Synthetic Cathinone

2015
Sudden cardiac death associated with methylone use.
    The American journal of forensic medicine and pathology, 2013, Volume: 34, Issue:1

    The rise in popularity of "bath salts" as safe alternatives to MDMA (3,4-methylenedioxymethamphetamine), methamphetamine, and other illicit substances has resulted in increased scrutiny of the contents and toxicology associated with these products. We report a case of sudden death related to the synthetic cathinone methylone (3,4-methylenedioxy-N-methylcathinonmethylone) in a previously healthy 19-year-old man. Although several fatal case reports have been published involving methylone and other synthetic cathinones, this is the first reported case of sudden cardiac death associated with methylone use. Although lack of published data prevented a comparison of blood methylone concentrations between our case and existing reports, the amount of methylone we detected postmortem (0.07 mg/dL) is below those reported in MDMA-related fatalities. Our report suggests that methylone toxicity has been greatly underestimated by users of this synthetic cathinone.

    Topics: Alkaloids; Central Nervous System Stimulants; Death, Sudden, Cardiac; Designer Drugs; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Male; Methamphetamine; Molecular Structure; Substance-Related Disorders; Young Adult

2013
Cardiac infection and sepsis in 3 intravenous bath salts drug users.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2013, Volume: 56, Issue:11

    The street drug "bath salts" are psychoactive mixtures of cathinone derivatives. We report 3 cases of disseminated Staphylococcus aureus infection with cardiac involvement (2 endocarditis and 1 pericarditis), secondary to intravenous bath salts use.

    Topics: Adult; Alkaloids; Bacteremia; Designer Drugs; Endocarditis, Bacterial; Female; Humans; Illicit Drugs; Male; Methamphetamine; Pericarditis; Staphylococcal Infections; Staphylococcus aureus; Substance Abuse, Intravenous

2013
An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as "bath salts".
    Progress in neuro-psychopharmacology & biological psychiatry, 2013, Aug-01, Volume: 45

    Methylone (3,4-methylenedioxymethcathinone) is a new psychoactive substance and an active ingredient of "legal highs" or "bath salts". We studied the pharmacokinetics and locomotor activity of methylone in rats at doses equivalent to those used in humans.. Methylone was administered to male Sprague-Dawley rats intravenously (10mg/kg) and orally (15 and 30 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.. Oral administration of methylone induced a dose-dependent increase in locomotor activity in rats. The plasma concentrations after i.v. administration were described by a two-compartment model with distribution and terminal elimination phases of α=1.95 h(-1) and β=0.72 h(-1). For oral administration, peak methylone concentrations were achieved between 0.5 and 1h and fitted to a flip-flop model. Absolute bioavailability was about 80% and the percentage of methylone protein binding was of 30%. A relationship between methylone brain levels and free plasma concentration yielded a ratio of 1.42 ± 0.06, indicating access to the central nervous system. We have identified four Phase I metabolites after oral administration. The major metabolic routes are N-demethylation, aliphatic hydroxylation and O-methylation of a demethylenate intermediate.. Pharmacokinetic and pharmacodynamic analysis of methylone showed a correlation between plasma concentrations and enhancement of the locomotor activity. A contribution of metabolites in the activity of methylone after oral administration is suggested. Present results will be helpful to understand the time course of the effects of this drug of abuse in humans.

    Topics: Alkaloids; Animals; Biological Availability; Brain; Central Nervous System Stimulants; Dose-Response Relationship, Drug; Male; Methamphetamine; Motor Activity; Protein Binding; Rats

2013
Seizures and hyponatremia related to ethcathinone and methylone poisoning.
    Journal of medical toxicology : official journal of the American College of Medical Toxicology, 2012, Volume: 8, Issue:1

    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.. 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.. 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 ethcatinone (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.

    Topics: Adult; Alkaloids; Amphetamines; Female; Humans; Hyponatremia; Methamphetamine; Propiophenones; Rhabdomyolysis; Seizures; Selective Serotonin Reuptake Inhibitors; Young Adult

2012
"Bath salts"-induced psychosis and serotonin toxicity.
    The Journal of clinical psychiatry, 2012, Volume: 73, Issue:8

    Topics: Administration, Inhalation; Adult; Alkaloids; Catha; Central Nervous System Stimulants; Diagnosis, Differential; Emergency Service, Hospital; Female; Humans; Mental Status Schedule; Methamphetamine; Psychoses, Substance-Induced; Pyrrolidines; Serotonin; Serotonin Syndrome

2012
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