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Background: Individuals with substance use disorder (SUD) are characterized by loss of control in drug use, such as increased impulsivity. Methamphetamine and methcathinone are psychostimulants, the use of which is accompanied by a high level of impulsivity. Whether individuals with methamphetamine use disorder (MUD) and methcathinone use disorder (MCUD) differ in different aspects of impulsivity is unclear. Methods: We investigated impulsivity traits and behaviors in individuals with MUD and MCUD. The Barratt Impulsiveness Scale (BIS), Sensation Seeking Scale (SSS), and delay discounting task (DDT) were assessed in individuals with MUD and MCUD and in healthy controls (HCs); then, we performed network-based analysis and computational modeling to understand the potential differences among the three groups. Results: MUD subjects scored higher than MCUD subjects in terms of motor impulsivity, nonplanning impulsivity, and total BIS scores. The network analysis revealed that there were no significant differences between MUD and MCUD subjects in any centrality indices. The discount rate of MUD and MCUD subjects was significantly greater than that of HCs, whereas there was no difference in the discount rate between the two addiction groups. Conclusions: These findings suggest that MUD and MCUD participants differ in impulsivity traits but not in impulsive behaviors, implying that impulsive traits and behaviors represent different aspects of impulsivity [ABSTRACT FROM AUTHOR]

An unknown impurity was detected in in-house prepared ephedrine hydrochloride (HCl) 5 mg/mL prefilled sterilized syringes when applying a stability-indicating British Pharmacopoeia 2018 impurity method for ephedrine injection. Ultraviolet, chromatographic, mass spectral, and physicochemical methods were combined to identify the unknown impurity. The unknown impurity was identified as methcathinone, which is generated from ephedrine drug substance through an oxidation reaction. A formulation study, in which different process adjustments were tested, was carried out to reduce the amount of unknown impurity. Nitrogen gassing in combination with 0.05 M citrate buffer addition proved to be the most potent process adjustment in reducing methcathinone formation in ephedrine HCl 5 mg/mL prefilled sterilized syringes after 4 months of storage in the dark at room temperature (20 °C ± 5 °C). More detailed research on the long-term stability of the reformulated ephedrine HCl drug product is currently underway, with promising results for up to 9 months gathered already. [ABSTRACT FROM AUTHOR]

Methcathinone (MCAT) belongs to the designer drugs called synthetic cathinones, which are abused worldwide for recreational purposes. It has strong stimulant effects, including enhanced euphoria, sensation, alertness, and empathy. However, little is known about how MCAT modulates neuronal activity in vivo. Here, we evaluated the effect of MCAT on neuronal activity with a series of functional approaches. C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold, especially in sensory and motor cortices, striatum, and midbrain motor nuclei. In vivo single-unit recording and two-photon Ca2+ imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration. Notably, MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability, specifically during a natural movie stimulus. It improved the information-processing efficiency by enhancing the single-neuron coding capacity, suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants. [ABSTRACT FROM AUTHOR]

Substance use disorder (SUD) is characterized by continued drug use despite adverse consequences. Methcathinone is a new type of psychoactive substance that is associated with high excitement and impulsive behaviors. However, it is unclear if individuals with methcathinone use disorders (MCUD) are with impaired decision-making ability. We analyzed the task performance in 45 male MCUD subjects and 35 male matched healthy controls (HC) with intertemporal decision-making task. Constant sensitivity discounting model was used to estimate potential changes in both discounting rate and time sensitivity. The results showed that MCUD individuals exhibited a higher delay discounting rate (p = 0.003, Cohen's d = 0.683) and reduced sensitivity to time (p < 0.001, Cohen's d = 1.662). The delay discounting rate was correlated to the first age for drug use (r = − 0.41, p = 0.004), and the time sensitivity was negatively correlated with the duration of abstinence (r = − 0.31, p = 0.036). We conclude that MCUD individuals are with impaired decision-making ability and time perception disturbances. [ABSTRACT FROM AUTHOR]

Copyright of Forensic Science & Technology is the property of Institute of Forensic Science, Ministry of Public Security and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Methcathinone (MCAT) is a psychostimulant of abuse that can cause both persistent striatal dopaminergic and serotonergic, as well as hippocampal serotonergic, deficits. Evidence suggests that the rapid effects of stimulants that are structurally and mechanistically similar to MCAT on monoamine transporter function may contribute to the abuse liability and/or persistent monoaminergic deficits caused by these agents. Thus, effects of MCAT on 1) striatal dopamine (DA) transporter (DAT); and 2) striatal and hippocampal serotonin transporter (SERT) function, as determined in tissues from adult male rats, were assessed. As reported previously, a single administration of MCAT rapidly (within 1 hr) decreases striatal [3H]DA uptake. Similarly, incubation of rat synaptosomes with MCAT at 37℃ (but not 4˚C) decreased striatal [3H]DA uptake. Incubation with MCAT likewise decreased [3H]5HT but not vesicular [3H]DA uptake. MCAT incubation in vitro was without effect on [3H]DA uptake in striatal synaptosomes prepared from MCAT‐treated rats. The decrease in [3H]DA uptake caused by MCAT incubation: (a) reflected a decrease in Vmax, with minimal change in Km, and (b) was attenuated by co‐incubation with the cell‐permeable calcium chelator, N,N'‐[1,2‐ethanediylbis(oxy‐2,1‐phenylene)]bis[N‐[2‐[(acetyloxy)methoxy]‐2‐oxoethyl]‐1,1'‐bis[(acetyloxy)methyl] ester‐glycine (BAPTA‐AM), as well as the non‐selective protein kinase‐C (PKC) inhibitors bisindolylmaleimide‐1 (BIM‐1) and 2‐[1‐3(Aminopropyl)indol‐3‐yl]‐3(1‐methyl‐1H‐indol‐3‐yl)maleimide (or Bisindolylmaleimide VIII; Ro‐31‐7549). Taken together, these results suggest that in vitro MCAT incubation may model important aspects of MCAT administration in vivo, and that calcium and PKC contribute to the in vitro effects of MCAT on DAT. [ABSTRACT FROM AUTHOR]

Rationale: The use of methcathinone (MCAT), a psychostimulant drug that can lead to long-term health risks and executive dysfunction, increased to an alarming rate in recent years. Impairments in low-level executive function have been reported in substance use disorder. However, little empirical evidence is available regarding high-level executive function (e.g., problem solving), which may act as a risk factor for relapse. Objectives: The present study aimed to investigate whether the problem-solving ability was altered in abstinent individuals with methcathinone use disorder (MCUD). Here, we tested fifty male MCUD individuals (short-term MCUD group: twenty-nine patients with MCAT use less than 3 years, long-term MCUD group: twenty-one patients with MCAT use longer than 3 years, which were split by medium years of drug use) and twenty-four well-matched healthy controls (HC) in the Tower of Hanoi task (TOH) to assess the impact of task difficulty on drug-related changes in problem-solving performance. We used several measures to characterize problem-solving performance: the number of mistakes made, the completion time of the task, and the thinking time before the first move. Results: In the low task difficulty condition, the MCUD group and HC group showed similar levels of mistakes and completion time, while in the high task difficulty condition, the MCUD group reported more mistakes (the mean number of mistakes in each trial: 1.41 ± 1.15 vs 0.79 ± 0.76, P = 0.019, Cohen's d = 0.635) and longer completion time in the task (the mean completion time in each trial: 45.83 ± 20.51 s vs 33.40 ± 15.10 s, P = 0.010, Cohen's d = 0.690) than the HC group. The thinking time before the first move did not differ significantly between groups (P = 0.257). We further found that the long-term (more than 3 years) MCUD group made more mistakes than the short-term MCUD group and HC group, mainly in the highly difficult subtasks. The longer time than HCs was reported in the long-term MCUD group among high task difficulty of subtasks. In addition, there was a positive correlation between years of MCAT use and the number of mistakes made in high task difficulty TOH task (r = 0.326, P = 0.021). Conclusions: Chronic methcathinone use was associated with deficits in problem-solving performance, which depended on the degree of task difficulty. The impairment was more evident in the long-term (> 3 years) MCAT group. [ABSTRACT FROM AUTHOR]

Objective To propose an alternative solid phase extraction-gas chromatography-mass spectrometry （SPE-GC-MS） method for the sensitive determination of cathinones in human urine samples, plus methodological verification. Methods Human urine samples were concentrated by solid phase extraction （SPE） sorbent and converted into the corresponding heptafluorobutyric acid anhydride derivatives. Methcathinone, 4-methyl methcathinone and 3,4-methylenedioxy-N-methylcathinone were detected by gas chromatography-mass spectrometry （GC-MS）. With quantitative analysis by internal standard method, methodological verification was carried out from the aspects of specificity, precision and reco-very rate. Results Methcathinone, 4-methyl methcathinone and 3,4-methylenedioxy-N-methylcathinone showed good linearly in the range of 25-200 ng/mL of urine （r>0.99）, with the limits of detection 2.0 ng/mL, limit of quantitation 25.0 ng/mL, both intra- and inter-day coefficients of variation lower than 6.0%, and recovery rates of 98.4%-105.7%. Conclusion The proposed SPE-GC-MS procedure has good accuracy and specificity, can meet the need of qualitative and quantitative analysis of cathinones in the urine of drug abusers, and therefore provide technical support for the detection of cathinone abuse.

Methcathinone, a new cathinone designer drug, which is structurally similar to amphetamine analogs, is a central nervous stimulant. Recently, there has been a worldwide rise in its popularity and abuse, and a growing number of cases with disability or even death is reported in several countries, resulting in public concern. The typical symptoms include accelerated heartbeat, high temperature, anxiety, depression, etc. Forensic studies on its toxicity mechanism are rare. This article reviews its toxicological effects, poisoning symptoms, poisoning and addiction mechanisms, and detection methods, to provide theoretical reference for future studies and guidance for related forensic identification.

The illicit supply of new psychoactive substances (NPS) in and from China has become a global concern. In line with the international prohibitionist regime, China has instituted a "zero tolerance" supply reduction policy, enacted various laws to regulate controlled substances, and punished related criminal behaviors severely. However, how the NPS supply is organized and how the national laws are interpreted and implemented at the local level have rarely been addressed. Data from qualitative interviews with governmental and judicial actors are used to investigate the experiences concerning the illicit supply of methcathinone and the dynamic ways in which drug policy and laws are implemented practically. Findings show the significance of Changzhi city as a distribution center for illicit supply of methcathinone, the fixed supply patterns, the prioritized measures for controlling methcathinone supply and demand, and the personal strategies used by individual actors to cope with political pressures and job requirements. This study concludes that the unbalanced coexistence of campaign-style and conventional governance results in active institutional arrangements and passive personal strategies in implementing the drug policy and further contributes to a discrepancy between policy formulation and its implementation in practice. [ABSTRACT FROM AUTHOR]

Background: A number of cases of severe parkinsonism-dystonia have been recognized and reported following the illicit use of ephedrone prepared from pseudoephedrine and potassium permanganate. The pathology associated with ephedrone neurotoxicity has not been described yet in the scientific literature.Objectives: To report the first neuropathological study of ephedrone toxicity.Methods: The brain of a 33-year-old Ukrainian female ex-ephedrone addict with a long history of l-dopa-unresponsive parkinsonism with dysarthria, dystonia, profound postural instability, cock-gait, and frequent falls, and on antiretroviral treatment, was examined using routine stains and immunohistochemistry.Results: Neuropathological findings included diffuse pallidal astrogliosis without neuronal depletion. There was also widespread vascular pathology with small vessels occluded by foreign material, associated with giant cell response without any evidence of consequent focal infarction and a cerebellar abscess.Conclusions: Clinical findings of l-dopa-unresponsive parkinsonism with dystonia, caused by illicit use of ephedrone, are fully consistent with neuropathological changes in the pallidum, lack of change in the SN, and preserved tyrosine hydroxylase activity. The findings in the basal ganglia are compatible with manganese toxicity. The vascular pathology is likely a joint effect of infection and the ephedrone toxicity on the vessels. © 2020 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of prenatal and lactational methcathinone exposure on the development and the learning and memory abilities of rat offspring using a Sprague-Dawley rat model. Pregnant and lactating rats were administered a consecutive daily dose of methcathinone (0.37 mg/kg) or an equivalent volume of saline by injection on gestational days 7–20 and postnatal days 2–15, respectively. The physical development and neurobehavioral test results of rat pups were recorded throughout the lactation period. Morris water maze (MWM) and novel object recognition (NOR) tests were performed from postnatal day 35 to day 42 to assess the learning and memory abilities of rat offspring in adolescence. The occurrence of hair growth and developments in neurological reflexes, such as improvements in limb grasp, righting reflex, and gait, were delayed in pups after perinatal methcathinone exposure compared with that in the control. Results from MWM and NOR tests indicate that perinatal methcathinone exposure induced deficits in spatial memory, learning ability, and novel object exploration in the adolescent offspring compared with that in the control. The impairment of spatial learning and memory was greater in the prenatal exposure group, while the impairment of novel object exploration was greater in the lactational exposure group. These data show that the prenatal and lactational methcathinone exposure induced the delay of physical and neurological reflex development and impaired learning and memory in rat offspring. [ABSTRACT FROM AUTHOR]

An irreversible extrapyramidal syndrome occurs in man after intravenous abuse of "homemade" methcathinone (ephedrone, Mcat) that is contaminated with manganese (Mn) and is accompanied by altered basal ganglia function. Both Mcat and Mn can cause alterations in nigrostriatal function but it remains unknown whether the effects of the 'homemade' drug seen in man are due to Mcat or to Mn or to a combination of both. To determine how toxicity occurs, we have investigated the effects of 4-week intraperitoneal administration of Mn (30 mg/kg t.i.d) and Mcat (100 mg/kg t.i.d.) given alone, on the nigrostriatal function in male C57BL6 mice. The effects were compared to those of the 'homemade' mixture which contained about 7 mg/kg of Mn and 100 mg/kg of Mcat. Motor function, nigral dopaminergic cell number and markers of pre- and postsynaptic dopaminergic neuronal integrity including SPECT analysis were assessed. All three treatments had similar effects on motor behavior and neuronal markers. All decreased motor activity and induced tyrosine hydroxylase positive cell loss in the substantia nigra. All reduced 123I-epidepride binding to D2 receptors in the striatum. Vesicular monoamine transporter 2 (VMAT2) binding was not altered by any drug treatment. However, Mcat treatment alone decreased levels of the dopamine transporter (DAT) and Mn alone reduced GAD immunoreactivity in the striatum. These data suggest that both Mcat and Mn alone could contribute to the neuronal damage caused by the 'homemade' mixture but that both produce additional changes that contribute to the extrapyramidal syndrome seen in man. [ABSTRACT FROM AUTHOR]

Methcathinone, a psychoactive substance with stimulant properties, has raised concerns in recent years due to its presence in urine screenings, even among individuals with no history of drug abuse. To prevent misjudgment, this work aims to explore the source of methcathinone in urine. A total of 58 urine samples tested positive for methcathinone in the National Taiwan University Hospital cohort, with 27 linked to illicit drug use and 31 from individuals with no drug use history. Co-occurrence analysis revealed a strong association between methcathinone and over-the-counter cold medications containing pseudoephedrine or ephedrine. In an in vivo experiment, participants who consumed pseudoephedrine-containing drugs showed the presence of methcathinone in their urine, suggesting a connection between these substances. Additionally, tests on pharmaceutical products containing pseudoephedrine detected small amounts of methcathinone as impurities. The findings suggest that the presence of methcathinone in nonillicit drug users may be attributed to impurities in over-the-counter pseudoephedrine-containing medications. This raises concerns about potential misinterpretations of drug screening results and underscores the need for more comprehensive criteria for assessing drug use. This study contributes to our understanding of the origin of methcathinone in urine, which has implications for legal justice and drug screening practices. [Display omitted] • Methcathinone was detected in urine drug screening results. • The origin of methcathinone in urine remains unclear. • Pseudoephedrine exhibited a strong correlation with the presence of methcathinone. • Methcathinone was discovered as an impurity in pseudoephedrine-containing pharmaceuticals. • The presence of drug impurities underscores the importance of interpreting drug screening results. [ABSTRACT FROM AUTHOR]

Copyright of Current Neurology / Aktualno?ci Neurologiczne is the property of Medical Communications Sp. z o.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of methcathinone and its metabolite cathinone in gastric contents. Methods: Proadifen hydrochloride (SKF525A) was used as internal standard. Column Eclipse Plus C18 column 1.8 μm, 100 mm× 3 mm was used as stationary phase. Mobile phase was 0.1 % formic acid aqueous solution and acetonitrile, gradient elution with flow rate of 0.3 mL/min and injection volume of 1 μL. Electrospray ion source (ESI) was detected by positive ion multi reaction monitoring mode MRM. Results: The linear range of methcathinone in gastric contents was 1-5000 ng/g, and the standard curve equation was Y=0.026X+0.4501 R²=0.9998, the detection limit was 0.5 ng/g, and the quantitative limit was 1.0 ng/g. The linear range of cathinone in gastric contents was 2-5000 ng/g, and the standard curve equation was Y=0.0099X+0.1576 R²=0.9997, the detection limit was 1.0 ng/g, and the quantitative limit was 2.0 ng/g. Conclusion: The established method for the detection of methcathinone and its metabolite cathinone in the gastric contents is simple and sensitive. This method can be used for the detection of methcathinone poisoning in the public security. [ABSTRACT FROM AUTHOR]

A method of high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the detection of methcathinone and its metabolite cathinone. Methcathinone was administered to rabbits by intravenous injection and gavage respectively. The blood of poisoned rabbits was collected at 1, 2, 4, 6 and 8 h after the administration. Then, the blood samples were extracted by internal standard proadifen hydrochloride (SKF525A) acetonitrile solution, and the extract was filtered with 0.22 μm organic filter membrane and detected by HPLC-MS/MS. The Column Eclipse Plus C18 chromatographic column (100 mm×3 mm×1.8 μm) was adopted and the column temperature was 45 °C, mobile phase was 0.1% formic acid aqueous solution and acetonitrile. The results of the rabbit experiment showed that after intravenous injection and gavage of methcathinone, the blood levels of methcathinone and its metabolite cathinone reached the peak within 1 h, and then gradually decreased. The peak value of methcathinone in the blood of intravenous administration was much higher than that of intragastric administration, while the peak value of metabolite cathinone was not significantly affected by the administration method. In addition, the elimination rate of methcathinone and its metabolite in blood of intravenous administration was significantly higher than that of gavage administration, and the content of methcathinone in blood 8 h after intravenous administration was lower than the detection limit. The linear relationship of methcathinone was good in the range of 0.2-2 000 μg/L, and the linear equation was y=0.014 1x+0.140 6 (r=0.999). The detection limit was 0.1 μg/L, the average recovery was 90.5%-98.5% in the concentration range of 0.5-500 μg/L. The intra-day RSD was 5.9%-7.9% and the inter-day RSD was 6.6%-8.8%. The linear relationship of cathinone was good in the range of 0.5-2 000 μg/L, and the linear equation was y=0.007 1x-0.023 1 (r=0.999), the detection limit was 0.2 μg/L, the average recovery was 90.2%-97.6% in the concentration range of 0.5-500 μg/L. The intra-day RSD was 5.7%-8.2% and the inter day RSD was 6.5%-9.1%. The method is simple and sensitive, and can be used to detect methoxyketone and its metabolite in blood samples. [ABSTRACT FROM AUTHOR]

Methcathinone (MC) and 3-fluoromethcathinone (3-FMC) are well-known members of the synthetic cathinone derivatives, the second most abused group of novel psychoactive substances (NPS). They are considered as methamphetamine-like cathinones, as they elicit their psychostimulatory effects via inhibition of monoamine uptake and enhanced release. The present study examines the effects of MC and 3-FMC on the spontaneous locomotor activity of mice and extracellular levels of dopamine and serotonin in the mouse striatum. Both MC and 3-FMC produced a dose-dependent increase of horizontal locomotor activity, but no significant changes in rearing behavior were observed. The locomotor stimulation induced by MC and 3-FMC is mediated by activation of dopaminergic neurotransmission, as selective D1-dopamine receptor antagonist, SCH 23390, abolished the effects of both drugs. In line with pharmacological data obtained by previous in vitro studies, MC and 3-FMC produced potent increases of extracellular dopamine and serotonin levels in the mouse striatum. Taken together, results presented within this study confirm previous findings and expand our knowledge on the pharmacology of MC and 3-FMC along with their behavioral effects. [ABSTRACT FROM AUTHOR]

Rationale: Mephedrone is a commonly abused constituent of "bath salts" and has many pharmacological effects in common with methamphetamine. Despite their structural similarity, mephedrone differs significantly from methamphetamine in its effects on core body temperature and dopamine nerve endings. The reasons for these differences remain unclear. Objectives: Mephedrone elicits a transient hypothermia which may provide intrinsic neuroprotection against methamphetamine-like toxicity to dopamine nerve endings. Furthermore, evidence in the literature suggests that this hypothermia is mediated by serotonin. By utilizing transgenic mice devoid of brain serotonin, we determined the contribution of this neurotransmitter to changes in core body temperature as well as its possible role in protecting against neurotoxicity. The effects of methcathinone and 4-methyl-methamphetamine, two structural analogs of mephedrone and methamphetamine, were also evaluated in these mice. Results: The hypothermia induced by mephedrone and methcathinone in wild-type mice was not observed in mice lacking brain serotonin. Despite preventing drug-induced hypothermia, the lack of serotonin did not alter the neurotoxic profiles of the test drugs. Conclusions: Serotonin is a key mediator of pharmacological hypothermia induced by mephedrone and methcathinone, but these body temperature effects do not contribute to dopamine nerve ending damage observed in mice following treatment with mephedrone, methcathinone or 4-methyl-methamphetamine. Thus, the key component of methamphetamine neurotoxicity lacking in mephedrone remains to be elucidated. [ABSTRACT FROM AUTHOR]

Rationale: Synthetic cathinones constitute a class of abused drugs that can act at dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT, respectively). Intracranial self-stimulation (ICSS) is a preclinical procedure that can be used to evaluate abuse potential of drugs, and prior studies have indicated that abuse-related ICSS effects of monoamine-transporter substrates, including some synthetic cathinones, are positively correlated with drug selectivity for DAT vs. SERT. Abuse potential of drugs can also be influenced by regimens of repeated drug exposure, but the role of repeated exposure on abuse-related ICSS effects of synthetic cathinones has not been examined. Objectives: This study used ICSS to evaluate effects of repeated treatment with the DAT>SERT substrate methcathinone, the DAT

Background: The appearance of stimulant-class new psychoactive substances (NPS) is a frequent and significant problem in our society. Cathinone variants are often sold illegally as 3,4-methylenedioxy methamphetamine ("ecstasy") or disguised for legal sale using misleading names such as "bath salts" and carry the risk of promoting disruptive mental states, addiction, and fatal overdose. The principal targets of these recreational drugs are monoamine transporters expressed in catecholaminergic and serotonergic neurons. Some transporter ligands can be transported into cells, where they can promote a massive release of neurotransmitters through reverse transport, and others can block uptake. A ligand's dopamine vs. serotonin transporter selectivity, potency, and activity as a substrate or blocker can help elucidate the abuse liability and subjective effects of a drug. Objectives: Here, we describe the discovery, development, and validation of an emerging methodology for compound activity assessment at monoamine transporters. Key findings: Substrates generate inward electrical currents through transporters and can depolarize the plasma membrane, whereas blockers work as a "cork in a bottle" and function as antagonists. Voltage-gated Ca2+ channels were co-expressed with monoamine transporters in cultured cells and used to measure fluctuations of the membrane electrical potential. In this system, substrates of monoamine transporters produce reliable dose-dependent Ca2+ signals, while blockers hinder them. Discussion: This system constitutes a novel use of voltage-gated Ca2+ channels as biosensors for the purpose of characterizing ligand activity at monoamine transporters using fluorimetry. This approach in combination with in vivo evaluations of drugs' abuse-related effects is a powerful strategy for anticipating potential stimulant-class NPS. [ABSTRACT FROM AUTHOR]

Hyperthermia is one of the severe acute adverse effects that can be caused by the ingestion of recreational drugs, such as methcathinones. The effect of hyperthermia on neurotoxicity is currently not known. The primary aim of our study was therefore to investigate the effects of hyperthermia (40.5 °C) on the neurotoxicity of methcathinone (MC), 4-chloromethcathinone (4-CMC), and 4-methylmethcathinone (4-MMC) in SH-SY5Y cells. We found that 4-CMC and 4-MMC were cytotoxic (decrease in cellular ATP and plasma membrane damage) under both hyper- (40.5 °C) and normothermic conditions (37 °C), whereby cells were more sensitive to the toxicants at 40.5 °C. 4-CMC and 4-MMC impaired the function of the mitochondrial electron transport chain and increased mitochondrial formation of reactive oxygen species (ROS) in SH-SY5Y cells, which were accentuated under hyperthermic conditions. Hyperthermia was associated with a rapid expression of the 70 kilodalton heat shock protein (Hsp70), which partially prevented cell death after 6 h of exposure to the toxicants. After 24 h of exposure, autophagy was stimulated by the toxicants and by hyperthermia but could only partially prevent cell death. In conclusion, hyperthermic conditions increased the neurotoxic properties of methcathinones despite the stimulation of protective mechanisms. These findings may be important for the understanding of the mechanisms and clinical consequences of the neurotoxicity associated with these compounds.

Background: Our previous research has shown that prenatal methcathinone exposure affects the neurodevelopment and neurobehavior of adolescent offspring, but the study on whether these findings continue into adulthood is limited., Objective: This study aims to explore the effects of prenatal methcathinone exposure on anxiety-like behavior, learning and memory abilities, as well as serum 5-hydroxytryptamine and dopamine concentrations in adult offspring., Methods: Pregnant rats were injected daily with methcathinone between the 7th and 20th days of gestation. The neurobehavioral performance of both male and female adult offspring rats was evaluated by neurobehavioral tests, including open-field tests, Morris water maze (MWM) tests, and novel object recognition (NOR) tests. The levels of 5-hydroxytryptamine and dopamine concentration in rat serum were detected by ELISA., Results: Significant differences were found in the length of center distance and time of center duration in the open-field test, as well as the times of crossing the platform in the MWM test, between the prenatal methcathinone exposure group and the control group. Results of the NOR test showed that adult offspring rats exposed to methcathinone need more time to discriminate the novel object. No gender differences were detected in the neurobehavioral tests. The serum concentrations of 5-hydroxytryptamine and dopamine in rats exposed to methcathinone prenatally were lower than that in the control group, and the serum dopamine concentration was independent of gender in each group., Conclusion: Prenatal methcathinone exposure affects the neurological behavior in adult offspring, and 5-hydroxytryptamine and dopamine might be involved in the process., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The synthetic cathinones are man-made compounds derived from the naturally occurring drug cathinone, which is found in the khat plant. The drugs in this pharmacological class that will be the focus of this chapter include mephedrone, MDPV, methcathinone and methylone. These drugs are colloquially known as "bath salts". This misnomer suggests that these drugs are used for health improvement or that they have legitimate medical uses. The synthetic cathinones are dangerous drugs with powerful pharmacological effects that include high abuse potential, hyperthermia and hyperlocomotion. These drugs also share many of the pharmacological effects of the amphetamine class of drugs including methamphetamine, amphetamine and MDMA and therefore have high potential to cause damage to the central nervous system. The synthetic cathinones are frequently taken in combination with other psychoactive drugs such as alcohol, marijuana and the amphetamine-like stimulants, creating a situation where heightened pharmacological and neurotoxicological effects are likely to occur. Despite the structural features shared by the synthetic cathinones and amphetamine-like stimulants, including their actions at monoamine transporters and receptors, the effects of the synthetic cathinones do not always match those of the amphetamines. In particular, the synthetic cathinones are far less neurotoxic than their amphetamine counterparts, they produce a weaker hyperthermia, and they cause less glial activation. This chapter will briefly review the pharmacology and neurotoxicology of selected synthetic cathinones with the aim of delineating key areas of agreement and disagreement in the literature particularly as it relates to neurotoxicological outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Copyright of Journal of Forensic Medicine / Fayixue Zazhi is the property of Journal of Forensic Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Methcathinone‐induced Parkinsonism is a recently described extrapyramidal syndrome characterized by globus pallidus and substantia nigra lesions, which provides a unique model of basal ganglia dysfunction. We assessed motivated behaviour in this condition using a novel cost‐benefit decision‐making task, in which participants decided whether it was worth investing effort for reward. Patients showed a dissociation between reward and effort sensitivity, such that pallidonigral complex dysfunction caused them to become less sensitive to rewards, while normal sensitivity to effort costs was maintained. [ABSTRACT FROM AUTHOR]

Methamphetamine and mephedrone are designer drugs with high abuse liability and they share extensive similarities in their chemical structures and neuropharmacological effects. However, these drugs differ in one significant regard: methamphetamine elicits dopamine neurotoxicity and mephedrone does not. From a structural perspective, mephedrone has a β-keto group and a 4-methyl ring addition, both of which are lacking in methamphetamine. Our previous studies found that methcathinone, which contains only the β-keto substituent, is neurotoxic, while 4-methylmethamphetamine, which contains only the 4-methyl ring substituent, elicits minimal neurotoxicity. In the present study, it was hypothesized that the varying neurotoxic potential associated with these compounds is mediated by the drug-releasable pool of dopamine, which may be accessed by methamphetamine more readily than mephedrone, methcathinone, and 4-methylmethamphetamine. To test this hypothesis, l -DOPA and pargyline, compounds known to increase both the releasable pool of dopamine and methamphetamine neurotoxicity, were combined with mephedrone, 4-methylmethamphetamine and methcathinone. Methamphetamine was also tested because of its ability to increase releasable dopamine. All three regimens significantly enhanced striatal neurotoxicity and glial reactivity for 4-methylmethamphetamine. Methcathinone neurotoxicity and glial reactivity were enhanced only by l -DOPA. Mephedrone remained non-neurotoxic when combined with either l -DOPA or pargyline. Body temperature effects of each designer drug were not altered by the combined treatments. These results support the conclusion that the neurotoxicity of 4-methylmethamphetamine, methcathinone and methamphetamine may be differentially regulated by the drug-releasable pool of dopamine due to β-keto and 4-methyl substituents, but that mephedrone remains non-neurotoxic despite large increases in this pool of dopamine. This article is part of the Special Issue entitled ‘Designer Drugs and Legal Highs.’ [ABSTRACT FROM AUTHOR]

In this study, a passive sampling technique, diffusive gradients in thin films (DGT) was developed to simultaneously measure two drugs, methcathinone (MC) and ephedrine (EPH) in surface water. Four types of binding gels and four types of filter membranes were tested for the optimal configuration. XAD18 agarose binding gel and agarose diffusive gel, together with polyethersulfone filter membrane were used for measuring MC and EPH in the DGT device. 5% NH 3 in acetonitrile was used as the elution solvent, with the elution efficiency for MC and EPH higher than 71%. At 25 °C, the diffusion coefficients of MC and EPH in the diffusive gel were 7.60 × 10 − 6 cm 2 s − 1 and 6.62 × 10 − 6 cm 2 s − 1 , respectively. The DGT was effective in a wide range of pH (4–11) and ionic strength (NaCl: 0.001–0.5 M). The DGT device was deployed in Beijing urban surface water for successive 7 days to measure the time-weighted concentrations of MC and EPH. Results showed that EPH was detected in all samples, while MC was below its detection limit. DGT concentrations were comparable to the concentrations determined by SPE. This study demonstrated that the developed DGT method was effective to monitor the two drugs in surface water in situ . [ABSTRACT FROM AUTHOR]

Mcthcathinone (ephcdrone) is an illicit stimulant drug which can be easily synthesized from pseudoephedrine, potassium permanganate and acetic acid. Mcthcathinone causes euphoria and, like methamphetamine, has effects on monoamines turnover in the brain and stimulates the release of dopamine into the synaptic cleft. Recently, more and more reports have been published on parkinsonism among mcthcathinone users, pathogenesis of which is associated with manganese neurotoxicity. The clinical picture includes dysarthria, postural instability with frequent falls, "cock-gait", parkinsonian signs (bradykincsia, hypomimia, extrapyramidal rigidity), bradyphrenia, hypersomnia, myoclonus, and autonomic failure (impotence, hypersalivation, seborrhea). Mn-induced parkinsonism is unresponsive to levodopa treatment. We describe a clinical case of ephcdrone induced neurotoxicity and present a brief literature review of its pathogenesis, symptoms, diagnosis, and possible treatment. [ABSTRACT FROM AUTHOR]

This work designed and synthesized novelly selective, highly efficient and friendly environmental biochar nanomaterial (ZMBC@ChCl-EG) by screening suitable deep eutectic solvent (DES) as the functional monomer via Density Functional Theory (DFT). The prepared ZMBC@ChCl-EG achieved the highly efficient adsorption of methcathinone (MC) and exhibited excellent selectivity as well as good reusability. Selectivity analysis concluded that the distribution coefficient value (K D) of ZMBC@ChCl-EG towards MC was 3.247 L/g, which was about 3 times higher than that of ZMBC, corresponding to stronger selective adsorption capacity. The studies of isothermal and kinetics indicated that ZMBC@ChCl-EG had an excellent adsorption capacity towards MC and the adsorption was mainly chemically controlled. In addition, DFT was used to calculate the binding energies between MC and each component. The binding energies were −10.57 kcal/mol for ChCl-EG/MC, −3.15∼-9.51 kcal/mol for BCs/MC, −2.33 kcal/mol for ZIF-8/MC, respectively, suggesting that DES played a major role in enhancing methcathinone adsorption. Lastly, the adsorption mechanisms were revealed by variables experiment combined with characterizations and DFT calculation. The main mechanisms were hydrogen bonding and π-π interaction. [Display omitted] • DFT calculation was exploited to design an adsorbent in this work. • Novelly selective, highly efficient and friendly environmental ZMBC@ChCl-EG by screening suitable DES was fabricated. • The adsorption mechanisms were explored by combining variables experiment with characterization as well as DFT calculation. • ZMBC@ChCl-EG achieved high efficiency and excellent selective adsorption for methcathinone. • The outstanding performance of ZMBC@ChCl-EG was due to hydrogen bonding and π-π interaction. [ABSTRACT FROM AUTHOR]

Khat is a common plant that grows primarily in Eastern Africa and the Arabian Peninsula. Cathinone, norpseudoephedrine, and norephedrine are the main psychoactive components of khat. Experimental studies have shown that red and green khat have similar cathinone contents, but green khat contains more norpseudoephedrine and norephedrine than red khat. Research indicates that Ethiopians believe that red khat has stronger psychoactive effects than green khat. Therefore, we speculated that other substances in red khat may enhance its psychoactive effects. Using the sampling method, we identified two other psychoactive components in khat: methcathinone and ethcathinone. At present, only a few studies on the extraction and detection of alkaloids from khat have been published in China, and no reports on the extraction and detection of methcathinone and ethcathinone from khat are available. In this study, we established an extraction and detection method for five alkaloids in dried khat using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS). To establish the extraction method, we optimized the extraction solvent and process. The amounts of dichloromethane and sodium hydroxide added during the purification step were also optimized. To establish the detection method, we optimized the chromatographic and MS conditions. The final extraction and detection method was as follows: Dried khat powder (0.1 g) was loaded into a polypropylene centrifuge tube, added with 1 mL of 0.05 mol/L hydrochloride aqueous solution, and vortex-oscillated for 3 min for extraction. The sample was centrifuged at 10000 r/min for 3 min. Next, 600 μL of the supernatant was placed in a centrifuge tube, added with 1 mL of dichloromethane, shaken for 1 min, and centrifuged at 10000 r/min for 3 min. Subsequently, 300 μL of the supernatant was placed in a centrifuge tube, added with 80 μL of 1 mol/L sodium hydroxide aqueous solution, shaken for 1 min, and added with 1 mL of acetonitrile. Vortex oscillation was performed for 2 min to extract the sample, after which solid sodium chloride (0.4 g) was added to the mixture, followed by shaking for 1 min to separate the acetonitrile and aqueous phases. The mixture was then centrifuged at 10000 r/min for 3 min. Finally, the supernatant was collected and diluted for further testing. The five target analytes were separated on a ZORBAX Eclipse Plus Phenyl-Hexyl column (100 mm×3.0 mm, 1.8 μm) via gradient elution using 0.1% acetic acid aqueous solution and acetonitrile as mobile phases with a flow rate of 0.3 mL/min and column temperature of 30 ℃. The analytes were identified using the targeted MS/MS method under positive electrospray ionization mode and quantified using the external standard method. The five alkaloids showed good correlations (all correlation coefficients ( r 2 )≥0.9976) with their respective linear ranges. The limits of detection were between 0.08 and 0.75 μg/L, and the limits of quantification were between 0.25 and 2.50 μg/L. The average recoveries of the five alkaloids from two plants with different alkaloid contents were between 90.7% and 105.2%. The intra-sample precision ranged from 0.5% to 2.3%, the intra-day precision was between 1.0% and 2.5%, and the inter-day precision was between 1.3% and 3.3%. Using the developed method, we extracted and analyzed 15 khat samples, and detected five alkaloids. This method enables rapid sample pretreatment and has high sensitivity, good stability, and suitable accuracy. Based on the above results, we conclude that the proposed method meets the inspection and identification requirements for khat. Thus, it can provide a valuable reference for the physical and chemical identification of khat and support for further studies on its psychoactive components.

[Display omitted] • VCD spectroscopy as a powerful tool to distinquish structurally similar substances. • Detailed 3D structures of two new synthetic cathinones. • The stabilizing hydrogen bond was revealed. • The development of enantioseparation protocol and methodology for detailed structural analysis. Recently, the number of structural modifications of synthetic cathinones has been growing making them the second largest group of new psychoactive substances in Europe. Although they are abused because of their various psychoactive effects, some compounds from this group also serve as pharmaceuticals. Since synthetic cathinones are chiral molecules with one chiral center, their biological, toxicological, and pharmacological properties may significantly differ according to their absolute configuration and enantiomeric excess. In this study, we have synthesized two substances bearing a pharmacologically interesting trifluoromethyl group and developed a chiral liquid chromatography method using a polysaccharide chiral stationary phase to separate the corresponding enantiomers of both these drugs. Subsequently, we utilized molecular spectroscopic methods including chiroptical (electronic circular dichroism and vibrational circular dichroism) and non-polarizable (infrared and ultraviolet absorption) spectroscopies. In combination with density functional theory calculations, we have obtained stable conformers of selected enantiomers in solution and their relative abundances, which we used to simulate their spectra. The experimental and calculated data have been used to elucidate the 3D structure of the enantiomerically pure compounds and assign the absolute configuration of all prepared compounds. [ABSTRACT FROM AUTHOR]

Intravenous use of a psychostimulant drug containing methcathinone (ephedrone) and manganese causes an irreversible extrapyramidal syndrome in drug abusers. We aimed to reproduce the syndrome in mice to evaluate dopaminergic damage. C57/B6 mice were intraperitoneally injected once a day with the study drug or saline for a period of 27 weeks. Motor activity was recorded in an automated motility-box. After 13 and 27 weeks of treatment, ex vivo digital autoradiography was performed using [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ). After 27 weeks of treatment [ 11 C]DTBZ autoradiography demonstrated a significant increase in the striatum-to-cerebellum binding ratio compared with saline treated controls. At the same time point, there was no evident change in motor activity. Increased [ 11 C]DTBZ binding may indicate vesicular monoamine transporter type 2 (VMAT2) function is altered. The lack of extrapyramidal symptoms in animals could be attributed to low dosing regimen or high metabolic rate. [ABSTRACT FROM AUTHOR]

Background A permanent Parkinsonian syndrome occurs in intravenous abusers of the designer psychostimulant methcathinone (ephedrone). It is attributed to deposition of contaminant manganese, as reflected by characteristic globus pallidus hyperintensity on T1-weighted MRI. Methods We have investigated brain structure and function in methcathinone abusers ( n = 12) compared to matched control subjects ( n = 12) using T1-weighted structural and resting-state functional MRI. Results Segmentation analysis revealed significant ( p < .05) subcortical grey matter atrophy in methcathinone abusers within putamen and thalamus bilaterally, and the left caudate nucleus. The volume of the caudate nuclei correlated inversely with duration of methcathinone abuse. Voxel-based morphometry showed patients to have significant grey matter loss ( p < .05) bilaterally in the putamina and caudate nucleus. Surface-based analysis demonstrated nine clusters of cerebral cortical thinning in methcathinone abusers, with relative sparing of prefrontal, parieto-occipital, and temporal regions. Resting-state functional MRI analysis showed increased functional connectivity within the motor network of patients ( p < .05), particularly within the right primary motor cortex. Conclusion Taken together, these results suggest that the manganese exposure associated with prolonged methcathinone abuse results in widespread structural and functional changes affecting both subcortical and cortical grey matter and their connections. Underlying the distinctive movement disorder caused by methcathinone abuse, there is a more widespread pattern of brain involvement than is evident from the hyperintensity restricted to the basal ganglia as shown by T1-weighted structural MRI. [ABSTRACT FROM AUTHOR]