Structure-Activity Relationship of Synthetic Cathinones: An Updated Review.

The escalating prevalence of new psychoactive substances (NPSs) poses a significant public health challenge, evidenced by the vast chemical diversity, with over 500 substances reported annually to the United Nations Office on Drugs and Crime-Early Warning Advisory (UNODC-EWA) in the past five years. Among NPSs, synthetic cathinones are gaining a lot of popularity among users. Notably, synthetic cathinones accounted for approximately 50% of the total quantity of NPSs reported as seized by EU Member States in 2021.

Sex differences in the effects of N-ethylpentylone in young CD1 mice: Insights on behaviour, thermoregulation and early gene expression.

Background And Purpose: New psychoactive substances such as N-ethylpentylone (NEP) are continuously emerging in the illicit drug market, and knowledge of their effects and risks, which may vary between sexes, is scarce. Our present study compares some key effects of NEP in male and female mice.

Experimental Approach: Psychostimulant, rewarding and reinforcing effects were investigated by tracking locomotor activity, conditioned place preference (CPP) paradigm and through a self-administration (SA) procedure, respectively, in CD1 mice.

Structure-Activity Relationship of -Ethyl-Hexedrone Analogues: Role of the α-Carbon Side-Chain Length in the Mechanism of Action, Cytotoxicity, and Behavioral Effects in Mice.

Synthetic cathinones are β-keto amphetamine derivatives whose appearance has increased dramatically in the past decades. -Ethyl substituted cathinones have been proven to potently inhibit dopamine (DA) uptake and induce psychostimulant and rewarding effects in mice. However, little is known about the influence of the alpha-carbon side-chain length of -ethyl cathinones on their pharmacological and toxicological effects.

Methamphetamine Blocks Adenosine A Receptor Activation via Sigma 1 and Cannabinoid CB Receptors.

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A receptor (AR).

Effects of High-Fat Diet and Maternal Binge-Like Alcohol Consumption and Their Influence on Cocaine Response in Female Mice Offspring.

Background: Prenatal alcohol exposure is a leading cause of neurobehavioral and neurocognitive deficits collectively known as fetal alcohol spectrum disorders, including eating disorders and increased risk for substance abuse as very common issues. In this context, the present study aimed to assess the interaction between prenatal and lactation alcohol exposure (PLAE) and a high-fat diet (HFD) during childhood and adolescence.

Methods: Pregnant C57BL/6 mice underwent a procedure for alcohol binge drinking during gestation and lactation periods.

Effects of MDPV on dopamine transporter regulation in male rats. Comparison with cocaine.

Rationale: MDPV (3,4-methylenedioxypyrovalerone) is a synthetic cathinone present in bath salts. It is a powerful psychostimulant and blocker of the dopamine transporter (DAT), like cocaine. It is known that acute exposure to psychostimulants induces rapid changes in DAT function.

Adolescent exposure to MDMA induces dopaminergic toxicity in substantia nigra and potentiates the amyloid plaque deposition in the striatum of APPswe/PS1dE9 mice.

MDMA is one of the most used drugs by adolescents and its consumption has been associated with many psychobiological problems, among them psychomotor problems. Moreover, some authors described that early exposure to MDMA may render the dopaminergic neurons more vulnerable to the effects of future neurotoxic insults. Alzheimer disease (AD) is the main cause of dementia in the elderly and a percentage of the patients have predisposition to suffer nigrostriatal alterations, developing extrapyramidal signs.

Changes in CREB and deltaFosB are associated with the behavioural sensitization induced by methylenedioxypyrovalerone.

Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone which has recently emerged as a designer drug of abuse. The objective of this study was to investigate the locomotor sensitization induced by MDPV in adolescent mice, and associated neuroplastic changes in the nucleus accumbens and striatum through deltaFosB and CREB expression. Behavioural testing consisted of three phases: Phase I: conditioning regimen with MDPV (0.

The combination of ethanol with mephedrone increases the signs of neurotoxicity and impairs neurogenesis and learning in adolescent CD-1 mice.

A new family of psychostimulants, under the name of cathinones, has broken into the market in the last decade. In light of the fact that around 95% of cathinone consumers have been reported to combine them with alcoholic drinks, we sought to study the consequences of the concomitant administration of ethanol on mephedrone -induced neurotoxicity. Adolescent male Swiss-CD1 mice were administered four times in one day, every 2h, with saline, mephedrone (25mg/kg), ethanol (2; 1.

Concentrations of MDPV in rat striatum correlate with the psychostimulant effect.

3,4-methylenedioxypyrovalerone or MDPV is a synthetic cathinone with psychostimulant properties more potent than cocaine. We quantified this drug in the striatum after subcutaneous administration to rats. MDPV reached the brain around 5 min after its administration and peaked at 20-25 min later.

Alcohol enhances the psychostimulant and conditioning effects of mephedrone in adolescent mice; postulation of unique roles of D3 receptors and BDNF in place preference acquisition.

Background And Purpose: The psychostimulant mephedrone is often consumed in combination with alcohol (EtOH). This kind of drug consumption during adolescence is a matter of concern.

Experimental Approach: We studied, in adolescent CD-1 mice, whether EtOH could enhance the psychostimulant (locomotor acivity) and rewarding [conditioned place preference (CPP)] effects of mephedrone.

Neuronal changes and oxidative stress in adolescent rats after repeated exposure to mephedrone.

Mephedrone is a new designer drug of abuse. We have investigated the neurochemical/enzymatic changes after mephedrone administration to adolescent rats (3×25 mg/kg, s.c.

Serotonin is involved in the psychostimulant and hypothermic effect of 4-methylamphetamine in rats.

4-Methylamphetamine (4-MA) has recently emerged as a designer drug of abuse in Europe and it is consumed always with amphetamine. There have been reported some deaths and non-fatal intoxications related to 4-MA. We investigated the changes in locomotor activity and body temperature after 4-MA administration to male Sprague-Dawley rats.

Serotonergic impairment and memory deficits in adolescent rats after binge exposure of methylone.

Methylone is a cathinone derivative that has recently emerged as a designer drug of abuse in Europe and the USA. Studies on the acute and long-term neurotoxicity of cathinones are starting to be conducted. We investigated the neurochemical/enzymatic changes indicative of neurotoxicity after methylone administration (4 × 20 mg/kg, subcutaneously, per day with 3 h intervals) to adolescent rats, to model human recreational use.

3,4-Methylenedioxymethamphetamine enhances kainic acid convulsive susceptibility.

Kainic acid (KA) causes seizures and neuronal loss in the hippocampus. The present study investigated whether a recreational schedule of 3,4-methylenedioxymethamphetamine (MDMA) favours the development of a seizure state in a model of KA-induced epilepsy and potentiates the toxicity profile of KA (20 or 30mg/kg). Adolescent male C57BL/6 mice received saline or MDMA t.

Molecular basis of the selective binding of MDMA enantiomers to the alpha4beta2 nicotinic receptor subtype: synthesis, pharmacological evaluation and mechanistic studies.

The α4β2 nicotinic acetylcholine receptor (nAChR) is a molecular target of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug also known as ecstasy, and it modulates the MDMA-mediated reinforcing properties. However, the enantioselective preference of the α4β2 nAChR subtype still remains unknown. Since the two enantiomers exhibit different pharmacological profiles and stereoselective metabolism, the aim of this study is to assess a possible difference in the interaction of the MDMA enantiomers with this nAChR subtype.

Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.

Mephedrone is a drug of abuse marketed as 'bath salts". There are discrepancies concerning its long-term effects. We have investigated the neurotoxicity of mephedrone in mice following different exposition schedules.

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

Rationale: Methylone, a new drug of abuse sold as "bath salts," has similar effects to ecstasy or cocaine.

Objective: We have investigated changes in dopaminergic and serotoninergic markers, indicative of neuronal damage induced by methylone in the frontal cortex, hippocampus, and striatum of mice, according to two different treatment schedules.

Methods: Methylone was given subcutaneously to male Swiss CD1 mice at an ambient temperature of 26 °C.

Protracted treatment with MDMA induces heteromeric nicotinic receptor up-regulation in the rat brain: an autoradiography study.

Previous studies indicate that 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) can induce a heteromeric nicotinic acetylcholine receptor (nAChR, mainly of α4β2 subtype) up-regulation. In this study we treated male Sprague-Dawley rats twice-daily for 10 days with either saline or MDMA (7 mg/kg) and sacrificed them the day after to perform [(125)I]Epibatidine binding autoradiograms on serial coronal slices. MDMA induced significant increases in nAChR density in the substantia nigra, ventral tegmental area, nucleus accumbens, olfactory tubercle, anterior caudate-putamen, somatosensory, motor, auditory and retrosplenial cortex, laterodorsal thalamus nuclei, amygdala, postsubiculum and pontine nuclei.

MDMA enhances hippocampal-dependent learning and memory under restrictive conditions, and modifies hippocampal spine density.

Objectives: Addictive drugs produce forms of structural plasticity in the nucleus accumbens and prefrontal cortex. The aim of this study was to investigate the impact of chronic MDMA exposure on pyramidal neurons in the CA1 region of hippocampus and drug-related spatial learning and memory changes.

Methods And Results: Adolescent rats were exposed to saline or MDMA in a regime that mimicked chronic administration.

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

Introduction: 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.

Material And Methods: Methylone was administered to male Sprague-Dawley rats intravenously (10mg/kg) and orally (15 and 30 mg/kg).

Heteromeric nicotinic receptors are involved in the sensitization and addictive properties of MDMA in mice.

We have investigated the effect of nicotinic receptor ligands in the behavioral sensitization (hyperlocomotion) and rewarding properties (conditioned place preference paradigm, CPP) of 3,4-methylenedioxy-methamphetamine (MDMA) in mice. Each animal received intraperitoneal pretreatment with either saline, dihydro-β-erythroidine (DHβE, 1 mg/kg) or varenicline (VAR, 0.3 mg/kg), 15 min prior to subcutaneous saline or MDMA (5 mg/kg), for 10 consecutive days.

Comparative neuropharmacology of three psychostimulant cathinone derivatives: butylone, mephedrone and methylone.

Background And Purpose: Here, we have compared the neurochemical profile of three new cathinones, butylone, mephedrone and methylone, in terms of their potential to inhibit plasmalemmal and vesicular monoamine transporters. Their interaction with 5-HT and dopamine receptors and their psychostimulant effect was also studied.

Experimental Approach: Locomotor activity was recorded in mice following different doses of cathinones.

Interaction of mephedrone with dopamine and serotonin targets in rats.

Introduction: We described a first approach to the pharmacological targets of mephedrone (4-methyl-methcathinone) in rats to establish the basis of the mechanism of action of this drug of abuse.

Experimental Procedures: We performed in vitro experiments in isolated synaptosomes or tissue membrane preparations from rat cortex or striatum, studying the effect of mephedrone on monoamine uptake and the displacement of several specific radioligands by this drug.

Results: In isolated synaptosomes from rat cortex or striatum, mephedrone inhibited the uptake of serotonin (5-HT) with an IC ₅₀ value lower than that of dopamine (DA) uptake (IC ₅₀=0.