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The preclinical pharmacology of mephedrone; not just MDMA by another name
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The preclinical pharmacology of mephedrone; not just MDMA by another name
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The preclinical pharmacology of mephedrone; not just MDMA by another name
Federal government websites often end in. The site is secure. This review critically examines the preclinical data on mephedrone that have appeared over the last 2—3 years and, where relevant, compares the pharmacological effects of mephedrone in experimental animals with those obtained following MDMA administration. Both mephedrone and MDMA enhance locomotor activity and change rectal temperature in rodents. However, both of these responses are of short duration following mephedrone compared with MDMA probably because mephedrone has a short plasma half-life and rapid metabolism. Mephedrone appears to have no pharmacologically active metabolites, unlike MDMA. There is also little evidence that mephedrone induces a neurotoxic decrease in monoamine concentration in rat or mouse brain, again in contrast to MDMA. The effect on 5-HT release in vivo is more marked with mephedrone even though both drugs have similar affinity for the dopamine and 5-HT transporters in vitro. The profile of action of mephedrone on monoamine receptors and transporters suggests it could have a high abuse liability and several studies have found that mephedrone supports self-administration at a higher rate than MDMA. Overall, current data suggest that mephedrone not only differs from MDMA in its pharmacological profile, behavioural and neurotoxic effects, but also differs from other cathinones. These two compounds have stimulant properties and methcathinone was actually marketed in the USSR as an antidepressant in the s but became illegal in the USA and several other countries in the s following evidence of widespread abuse see Kelly, Bupropion, another chemically related compound, has been available in many countries since the mid s, being initially marketed as an antidepressant, a treatment for attention deficit hyperactivity disorder and subsequently as an aid to smoking cessation. However, the government announced on 3 July that it intended to make this herbal stimulant a controlled class C drug like anabolic steroids and ketamine. For a more detailed historical overview on the history of the synthesis and clinical use of cathinone derivatives, see Kelly Because of the extensive recreational use of mephedrone it received substantial media attention in the UK, particularly as it was implicated in a number of adverse events and unexplained deaths and was banned in April following the advice of the Advisory Committee on the Misuse of Drugs ACMD, This was perhaps a surprising conclusion given that we have been unable to find in PubMed a single preclinical neuropharmacological publication on mephedrone before and very few on methcathinone. There are no published formal studies assessing the psychological or behavioural effects of mephedrone in humans. In addition, there are no animal studies on which to base an extrapolation of potential effects. Interestingly, this law is similar to those enacted in Europe in that it covers many related cathinone substances. Before being banned, mephedrone was the cathinone derivative with the highest recreational use. Both the decline in purity and availability of ecstasy tablets and the fact that mephedrone had initially been legal are thought to be the main reasons for its increased popularity EMCDDA, What was striking about the legislation that made mephedrone illegal was the way it was constructed. In contrast, not only mephedrone but also many other chemically related cathinone compounds were also banned with it, presumably in an attempt to outlaw the development and use of structurally related designer drugs. It was believed that this was the first time that a generic ban based purely on chemical structure had been enforced on a group of compounds Morris, What many may consider should be a matter of some concern is that the ban on mephedrone and related compounds appeared to have been driven more by information given in the media rather than peer-reviewed scientific knowledge gained from relevant clinical and preclinical pharmacological studies. Many of the newspaper reports on the effects of the drug in recreational users were hyperbolic, speculative or just incorrect. Needless to say, retraction of the false information seldom occurred. No forensic blood samples were taken to confirm that exposure to mephedrone had occurred. The last 2—3 years has seen the publication of a reasonable body of preclinical work on the pharmacology of mephedrone and this review is a critical appraisal of these studies. What is now becoming clear is that mephedrone has its own very specific pharmacology that is distinct from MDMA and also other amphetamines. For simplicity, the information is grouped in subsections that examine its main pharmacokinetic and pharmacodynamic effects in experimental animals. Until recently, a major problem in assessing the pharmacological effects of MDMA was that few detailed pharmacokinetic studies had been performed in either animals or humans. Consequently, it was difficult to translate most of the preclinical pharmacodynamic studies of this drug in terms of their likely functional and toxicological importance. The normal routes of mephedrone administration in recreational users are reported to be oral and insufflation. Extrapolation from dosing to plasma levels is difficult as there are no detailed dose—concentration curves available and pharmacokinetic studies on the drug in humans have yet to be performed. However, this dose may not be sufficient to reflect the drug exposure that must occur when humans engage in binge dosing. In mimicking that situation, repeat dosing of animals must also be performed. In Sprague-Dawley rats, the uptake and elimination of a single dose of mephedrone 5. In binge dosing studies, plasma levels of Whole brain tissue levels of 2. A further study in Sprague-Dawley rats given i. A few investigations have examined the metabolic pathways of mephedrone in both rodents and man. Identification was primarily in plasma, but also in urine. The same metabolites were identified in human plasma and urine but additionally 4-carboxy-dihydro-mephedrone was also identified in urine. It is unclear at present whether any of the metabolites possess pharmacological activity. They also found both hydroxytolyl-mephedrone and nor-mephedrone were formed. In four forensic traffic accident cases where mephedrone was detected in blood, hydroxytolyl-mephedrone and nor-mephedrone, 4-carboxy-dihydro-mephedrone, dihydro-mephedrone, and 4-carboxy-mephedrone were all also detected. The major metabolites of mephedrone and proposed pathways of their formation. This distinction may explain why most studies have failed to observe any similar mephedrone-induced neurotoxicity in rat brain see later. Furthermore, this is consistent with the proposal that the general pharmacokinetic profile of mephedrone is similar in rats and humans. Increased locomotion following mephedrone administration has been observed in several strains of rats and mice. A subsequent study S. Although mephedrone increased locomotor activity for a similar duration in both strains, significantly more activity was observed in Sprague-Dawley rats. The locomotor activity was similar when the rats were examined in either ambient temperature condition, in contrast to the effect of mephedrone on body temperature see later. However, they also reported that no sensitization occurred in a parallel cohort given methamphetamine using the same dosing schedule. Both groups observed robust enhancement of the locomotor response on the final test day compared with that seen following the first injection. In contrast, both mephedrone and MDMA, neither of which has been reported to induce stereotypic behaviour, produced a monophasic, dose-dependent reduction in counts compared with saline-treated controls. Although such a decrease seems paradoxical when compared with the consistent increase in locomotion recorded in activity boxes, this is because spontaneous wheel running represents a different form of activity involving divergent behavioural processes from spontaneous activity. Interestingly, there is one clinical case report of the 5-HT syndrome in a mephedrone user, but the patient was also taking fluoxetine so it is likely that it is the combination that was responsible Garrett and Sweeney, Mephedrone administration also increases locomotor activity in mice. Pretreatment with p-chlorophenylalanine PCPA , an inhibitor of 5-HT synthesis, also reduced the hyperlocomotor effect of mephedrone. They also noted that D 2 receptor activation appeared to contribute to the repetitive circling behaviour produced by MDMA. These individuals sometimes also present with problems associated with hyperthermia, including rhabdomyolysis, myoglobinuria, renal failure, liver damage and disseminated intravascular coagulopathy, which can be fatal. Although administration of high or repeated doses of MDMA to rats usually causes hyperthermia, it can produce hypothermia particularly following a low dose or when the animals are housed singly or in a cool ambient temperature Docherty and Green, Nevertheless, both MDMA-induced hyper-and hypothermia result from monoamine release in the brain Docherty and Green, These reports confirm that cathinones have effects on temperature regulation at similar doses to those that affect locomotor behaviour. Consequently, these indications that mephedrone might be altering thermoregulation in humans, coupled with earlier reports that both cathinone and methcathinone administration produces hyperthermia in rodents, spurred several groups to examine in detail the effect of mephedrone on body temperature and thermoregulation in rats. Yet hyperthermia did not occur as would be expected with MDMA. Two recent studies found that repeated dosing of methedrone on the same day binge dosing induced hyperthermia. In contrast, in our own recent study on repeated dosing in individually housed rats, we again observed hypothermia S. Because both strains responded with a similar hypothermic response to the 5-HT 1A agonist 8-hydroxy di-n-propylamino tetralin 8-OH-DPAT , this suggests that there is a strain-specific difference in the body temperature response to mephedrone rather than some generalized difference in their ability to respond to temperature-changing drugs. In an attempt to further understand the mechanisms involved in the induction of hypothermia following mephedrone, several groups have investigated its effect on cardiovascular function. MDMA administered to singly housed rats at normal ambient temperature decreased tail temperature, indicative of peripheral vasoconstriction. Under these same conditions, mephedrone also produced hypothermia, but the small and short-lasting decrease in rectal temperature was associated with a prolonged decrease in tail temperature, and therefore differed from the temporal profile of MDMA-induced thermoregulatory response. Further evidence for an action of mephedrone on peripheral adrenergic mechanisms has been obtained by two investigations on cardiovascular function in the rat. The responses following s. They also examined the action of mephedrone on cardiac function in rats in real time using echocardiography. Mephedrone produced dose-dependent effects on the heart that were consistent with sympathomimetic stimulation. Ejection fraction and fractional shortening, both indicators of cardiac contractility, were also significantly increased. The effects of mephedrone on the heart after i. These results suggest that any cardiac stimulant actions of MDMA and mephedrone may involve indirect sympathomimetic effects. It is also possible that an increase in locomotor activity may increase heart rate, but this is unlikely in human studies on MDMA where low doses were given in controlled clinical conditions. Only two studies have been published on the effect of mephedrone on brain tissue monoamine concentrations measured shortly after drug administration. Dopamine was significantly elevated, while 5-HT was significantly decreased, in the striatum and hippocampus following a single dose. These results are similar to the acute effect of MDMA on cerebral monoamine content. Any discrepancies in the levels of monoamine or metabolites between studies are almost certainly due to rapid changes in their synthesis, release, metabolism and clearance shortly after drug-administration. Recently, we have found that mephedrone also increases the extracellular concentration of dopamine in the striatum S. This association of amphetamines with neurotoxic damage to amine nerve terminals in the brain encouraged several groups to examine whether mephedrone also induced neurotoxicity in the rodent brain. A dose schedule of 7. This methamphetamine dosing regime produced the expected dopamine neurotoxicity in the striatum, decreasing dopamine, DAT and tyrosine hydroxylase levels. Mephedrone failed to produce any neurotoxic damage, but enhanced the methamphetamine-induced dopamine neurotoxicity. Mephedrone also enhanced the neurotoxic effects of amphetamine and MDMA on dopamine nerve endings, suggesting that a potentially dangerous interaction might occur if mephedrone is taken either intentionally or unintentionally with other illicit amphetamines. Substrates but not blockers are transported into the cell where they disrupt vesicular storage and stimulate non-exocytotic monoamine release by reversing the transporter flux Rothman and Baumann, ; Sitte and Freissmuth, , and may also interact with vesicular monoamine transporters. Their results showed that mephedrone and MDMA cause non-selective release of monoamines by being substrates for all the transporters, while amphetamine is a selective substrate at both DAT and NET. Furthermore, mephedrone and MDMA both had a similar potency to each other as a releaser at all three monoamine transporters. Again, their results pointed to mephedrone functioning as a transportable substrate. However, meta-analysis does not suggest a clear dose-related association but implies that a combination of MDMA with other recreational drugs may be more problematic Verbaten, ; Laws and Kokkalis, Although MDMA had no influence on associative memory in the CER test, the highest dose of mephedrone significantly reduced freezing on re-exposure to the context used for conditioning, but had no effect on freezing produced by representation of the light and tone cue, suggesting mephedrone attenuated contextual but not cued association, which are mediated by different neuroanatomical substrates. In rhesus monkeys, a pronounced improvement in visual-spatial memory and learning occurred after a 0. Although repeated mephedrone did not cause any lasting changes in anxiety elevated plus maze or social preference, it caused a clear deficit in NOD 36 days after drug treatment. This risk contrasts with MDMA where users may suffer from some adverse events on acute withdrawal, but unequivocal reports of dependence or withdrawal are completely absent. The preference shift detected following mephedrone conditioning suggests that the drug displays rewarding properties consistent with a risk of abuse liability. However, this shift was only seen at a very high dose. Adult male mice with unipolar stimulating electrodes implanted in the lateral hypothalamus responded for varying frequencies of brain stimulation reward BSR. Cocaine dose-dependently lowered the EF 50 and threshold beginning immediately after administration, but did not affect maximum response rate. These results suggest that mephedrone, like cocaine, potentiates BSR, which the authors concluded may indicate its potential for abuse. Currently, very few studies have investigated possible interactions of mephedrone with other drugs. Our own preliminary study found that MDMA pre-exposure altered the subsequent temperature response to a challenge dose of mephedrone, suggesting cross-sensitivity of some functional responses in rats S. It also enhanced the neurotoxic effects of amphetamine and MDMA on dopamine neurons, suggesting that a potentially dangerous interaction might occur when mephedrone is taken with other recreational drugs. This combined action could have serious adverse effects on brain function. As detailed in the Introduction, although recreational users have stated that the psychoactive effects of mephedrone are similar to those of MDMA, the preclinical studies detailed in this review make it clear that these two drugs have a rather different, albeit related pharmacology. Mephedrone has some properties that suggest its adverse effect profile might be less than MDMA, but its use by humans still raises significant safety concerns. Data compiled to compare the behavioural effects and pharmacokinetic measurements were derived from studies using a single acute s. On the positive side, mephedrone, at least when given at a dose to rats that may have translational relevance, does not appear to induce monoamine neurotoxicity or produce hyperthermia in the majority of investigations. However, hyperthermia did occur when mephedrone was combined with caffeine. Of note are the indications that mephedrone has a short plasma half-life in rats and probably in humans, which is probably the reason why many recreational users take repeated doses over a short period. This binge use may induce more severe adverse consequences. What is also becoming clear from preclinical studies is that mephedrone has high-abuse liability resulting from several pharmacokinetic and pharmacodynamic differences from MDMA. Firstly, it has high brain penetration, rapid metabolism and brain clearance all of which are likely to lead to an acute withdrawal phenomenon. This does not occur with MDMA which has slower brain penetration, metabolism and clearance, both in rats and crucially in humans. Self-administration studies in rats show that mephedrone, unlike MDMA, robustly supports this behaviour. Emerging data suggest that, like amphetamine and its derivatives, the cathinones all have their own specific pharmacological profile. Consequently, the pharmacology of mephedrone reviewed here cannot be taken as a template for the properties of other illicit cathinone derivatives that are appearing. As a library, NLM provides access to scientific literature. Br J Pharmacol. Published online Apr E-mail: ku. Keywords: mephedrone, cathinones, MDMA, locomotion, body temperature, drug metabolism, dopamine, 5-hydroxytryptamine. Open in a separate window. Figure 1. Metabolism and pharmacokinetics of mephedrone in rats and humans Until recently, a major problem in assessing the pharmacological effects of MDMA was that few detailed pharmacokinetic studies had been performed in either animals or humans. Figure 2. Locomotor activity Increased locomotion following mephedrone administration has been observed in several strains of rats and mice. Figure 3. Figure 4. Figure 5. Effect on brain monoamine concentrations Only two studies have been published on the effect of mephedrone on brain tissue monoamine concentrations measured shortly after drug administration. Drug interactions Currently, very few studies have investigated possible interactions of mephedrone with other drugs. Conclusions As detailed in the Introduction, although recreational users have stated that the psychoactive effects of mephedrone are similar to those of MDMA, the preclinical studies detailed in this review make it clear that these two drugs have a rather different, albeit related pharmacology. Combinations of other drugs with either MDMA or mephedrone and have been reported to, respectively, enhance or induce toxicity as detailed in the text. Conflict of interest The authors declare no conflicts of interest. Mephedrone 4-methylmethcathinone supports intravenous self-administration in Sprague-Dawley and Wistar rats. Addict Biol. Effect of MDMA ecstasy on activity and cocaine conditioned place preference in adult and adolescent rats. Neurotoxicol Teratol. Consideration of the cathinones. Home office report. Effects of methylenedioxymethamphetamine on noradrenaline-evoked contractions of rat right ventricle and small mesenteric artery. Eur J Pharmacol. J Neurochem. Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA. Effects of combined treatment with mephedrone and methamphetamine or 3,4-methylenedioxymethamphetamine on serotonin nerve endings of the hippocampus. Life Sci. The neurotoxic effects of 3,4-methylenedioxymethamphetamine MDMA and methamphetamine on serotonin, dopamine, and GABA-ergic terminals: an in-vitro autoradiographic study in rats. Changes in cardiovascular responsiveness and cardiotoxicity elicited during binge administration of ecstasy. J Pharmacol Exp Ther. Psychopharmacology Berl ; — Drug Metab Dispos. The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Involvement of D1 dopamine receptor in MDMA-induced locomotor activity and striatal gene expression in mice. Brain Res. Contribution of impulsivity and novelty seeking to the acquisition and maintenance of MDMA self-administration. Repeated exposure to MDMA and amphetamine: sensitization, cross-sensitization, and response to dopamine D 1 -and D 2 -like agonists. Drug Test Anal. Instability of the ecstasy market and a new kid on the block: mephedrone. J Psychopharmacol. Neurotoxicity of substituted amphetamines: molecular and cellular mechanisms. Neurotox Res. Neurotoxicity of ecstasy metabolites in rat cortical neurons, and influence of hyperthermia. Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview. Mol Neurobiol. A web-based survey on mephedrone. Drug Alcohol Depend. Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus. Drug seeking in response to a priming injection of MDMA in rats: relationship to initial sensitivity to self-administered MDMA and dorsal striatal dopamine. Int J Neuropsychopharmacol. Heat increases 3,4-methylenedioxymethamphetamine self-administration and social effects in rats. Dopamine and norepinephrine in noradrenergic axons: a study in vivo of their precursor product relationship by mass fragmentography and radiochemistry. Pharmacol Rev. Cathinone: an investigation of several N-alkyl and methylenedioxy-substituted analogs. Pharmacol Biochem Behav. The pharmacology and toxicology of the synthetic cathinone mephedrone 4-methylmethcathinone Drug Test Anal. Mass-information: mephedrone, myths, and the new generation of legal highs. Drugs Alcohol Today. The role of monoamines in the changes in body temperature induced by 3,4-methylenedioxymethamphetamine MDMA, ecstasy and its derivatives. J Am Med Assoc. Mephedrone: public health risk, mechanisms of action, and behavioral effects. Annual report the state of the drugs problem in Europe. Report on the risk assessment of mephedrone in the framework of the Council Decision on new psychoactive substances. Substituted methcathinones differ in receptor and transported interactions. Biochem Pharmacol. Serotonin synthesis inhibition reveals distinct mechanisms of action for MDMA and its enantiomers in the mouse. New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. The serotonin syndrome as a result of mephedrone toxicity. BMJ Case Rep. Effects of drugs on the processes regulating the functional activity of brain 5-hydroxytryptamine. Lost in translation: preclinical studies on MDMA provide information on mechanisms of action, but do not allow accurate prediction of adverse events in humans. Mephedrone 4-methylmethcathinone , a principal constituent of psychoactive bath salts, produces behavioral sensitization in rats. TIME online. Morbidity associated with MDMA ecstasy abuse: a survey of emergency department admissions. Hum Exp Toxicol. Acute and long-term consequences of single MDMA administration in relation to individual anxiety levels in the rat. Behav Brain Res. Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain. Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats. Clin Pharmacol Ther. Clinical characteristics of mephedrone toxicity reported to the U. National Poisons Information Service. Emerg Med J. J Clin Psychiatry. Cathinone increases body temperature, enhances locomotor activity, and induces striatal c-fos expression in the Siberian hamster. Neurosci Lett. Mephedrone, compared with MDMA ecstasy and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. Cathinone derivatives: a review of their chemistry, pharmacology and toxicology. Measurement of immediate-early gene activation-c-fos and beyond. J Neuroendocrinol. Ecstasy MDMA and memory function: a meta-analytic update. Hum Psychopharmacol. Cardiovascular effects of 3,4-methylenedioxymethamphetamine: a double blind, placebo-controlled trial. Ann Intern Med. Comparative neuropharmacology of three psychostimulant cathinone derivatives: butylone, mephedrone and methylone. Differences between rats and mice in MDMA methylenedioxymethylamphetamine neurotoxicity. Interaction of mephedrone with dopamine and serotonin targets in rats. Eur Neuropsychopharmacol. Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics. Mephedrone 4-methylmethcathinone -related deaths. J Anal Toxicol. Tweaking, bombing, dabbing and stockpiling: the emergence of mephedrone and the perversity of prohibition. Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicol Lett. Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry. Anal Bioanal Chem. The role of temperature, stress, and other factors in the neurotoxicity of the substituted amphetamines 3,4-methylenedioxymethamphetamine and fenfluramine. Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone mephedrone Drug Alcohol Depend. Do novel psychoactive substances displace established club drugs, supplement them or act as drugs of initiation? The relationship between mephedrone, ecstasy and cocaine. Eur Addict Res. UK places generic ban on mephedrone drug family. Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion. High levels of intravenous mephedrone 4-methylmethcathinone self-administration in rats: neural consequences and comparison with methamphetamine. The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. Turnover rate measurements of brain serotonin in unanesthetized rats. Adv Biochem Psychopharmacol. Cardiovascular and sympathetic responses and reflex changes elicited by MDMA. Physiol Behav. Elevation of ambient room temperature has differential effects on MDMA-induced 5-HT and dopamine release in striatum and nucleus accumbens of rats. MDMA-induced neurotoxicity: long-term effects on 5-HT biosynthesis and the influence of ambient temperature. MDMA and 5-HT neurotoxicity: the empirical evidence for its adverse effects in humans — no need for translation. Neurosci Biobehav Rev. In vitro metabolism studies on mephedrone and analysis of forensic cases. Cutaneous vasoconstriction contributes to hyperthermia induced by 3,4-methylenedioxymethamphetamine ecstasy in conscious rabbits. J Neurosci. Memory deficit and reduced anxiety in young adult rats given repeated intermittent MDMA treatment during the periadolescent period. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. The role of alpha 2-adrenoceptors in the vasculature of the rat tail. Mephedrone toxicity in a Scottish emergency department. Methcathinone intoxication in the rat: abrogation by dextrorphan. Ann Emerg Med. Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats. Monoamine transporters and psychostimulant drugs. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. How the media helped ban mephedrone. Br Med J. MDMA self-administration in laboratory animals: a summary of the literature and proposal for future research. J Clin Psychopharmacol. Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia. Caffeine alters the behavioural and thermoregulatory responses to mephedrone without causing long-term neurotoxicity. Behavioural and neurochemical comparison of chronic intermittent cathinone, mephedrone and MDMA administration to the rat. Pharmacological characterization of designer cathinones in vitro. Mechanisms of MDMA ecstasy -induced oxidative stress, mitochondrial dysfunction, and organ damage. Curr Pharm Biotechnol. Comparative study of cathinone and amphetamine on brown adipose thermogenesis. Generic legislation of new psychoactive drugs. Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Drugs for youth via Internet and the example of mephedrone. Comparison of the behavioral and cardiovascular effects of mephedrone with other drugs of abuse in rats. Specific memory deficits in ecstasy users? The results of a meta-analysis. Opposite effects of 3,4-methylenedioxymethamphetamine MDMA on sensorimotor gating in rats versus healthy humans. Mephedrone: use, subjective effects and health risks. Mephedrone, new kid for the chop? Mephedrone 4-methylmethcathinone : what is new in our understanding of its use and toxicity. Prog Neuropsychopharmacol Biol Psychiatry. Case series of individuals with analytically confirmed acute mephedrone toxicity. Clin Toxicol Phila ; 48 — Clinical pattern of toxicity associated with the novel synthetic cathinone mephedrone. Limited use of novel psychoactive substances in South London nightclubs. Effect of ambient temperature on the thermoregulatory and locomotor stimulant effects of 4-methylmethcathinone in Wistar and Sprague-Dawley rats. Mephedrone 4-methylmethcathinone and d-methamphetamine improve visuospatial associative memory, but not spatial working memory, in rhesus macaques. Designer cathinones — an emerging class of novel recreational drugs. Forensic Sci Int. Copy Download. Locomotor activity 1—3 , Body temperature 4—6 , Drug self-administration 6 , Brain monoamine release in vivo 9—11 , Brain neurotoxicity 14—16 , Monoamine uptake inhibition IC 50 18, Monoamine release EC 50 20—22 ,
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