Amphetamine-like Drugs Research Articles

Augmentation of intracranial self-stimulation induced by amphetamine-like drugs in Period circadian regulator 2 knockout mice is associated with intracellular Ca2+ levels

Over the past decade, new psychoactive substances (NPS) have emerged in the illegal drug market and have continued to attract attention from the international community. Among these, amphetamine-like NPS, classified as stimulants, constitute a significant proportion. However, the pharmacological characteristics and mechanisms underlying addiction to amphetamine-like NPS remain poorly understood. Given that circadian rhythms are linked to the brain stimulation effects of methamphetamine (METH) and amphetamine, we investigated the effects of METH, 1-(4-methoxyphenyl)-N-methylpropan-2-amine (PMMA), and 1-(benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB) on intracranial self-stimulation (ICSS) in wild-type (WT) or Period circadian regulator 2 knockout mice. Amphetamine-like drugs increase intracellular Ca2+ levels to provoke dopamine release, so we examined the impact of Per2 knockdown on intracellular Ca2+ levels in PC12 cells to elucidate a potential mechanism underlying NPS-induced ICSS enhancement. Our ICSS results showed that METH and PMMA significantly increased brain stimulation in Per2 knockout mice compared to WT mice. Similarly, METH and PMMA induced higher Ca2+ fluorescence intensity in Per2 knockdown PC12 cells than in control cells. In contrast, 5-EAPB did not produce significant changes in either ICSS or Ca2+ signaling. These findings suggest that Per2 plays a crucial role in the brain stimulation effects of amphetamine-like drugs through the regulation of intracellular Ca2+.

Direct infusion mass spectrometric analysis of ephedrine and pseudoephedrine

For thousands years Ephedrae herba has been used in traditional Chinese herbal medicine. Its main bioactive constituents are ephedrine and pseudoephedrine. Nowadays, these alkaloids have found application in various clinical treatments, as sports-enhancing drugs and for the illicit production of amphetamine-like drugs. Ephedrine and pseudoephedrine are diastereomers, and because of their high polarity and similar pKa values, their chromatographic separation may be a challenge. In this study a possible application of direct infusion mass spectrometry and direct infusion tandem mass spectrometry has been proposed for differentiation of ephedrine and pseudoephedrine as well as the relative determination of the contents of these compounds in a mixture. At low collision energy condition, the ratio of relative abundances of ions [M+H–H2O]+ and [M+H]+ permit distinction of the analyzed diastereomers, and enable evaluation of their relative content in a mixture with no need of chromatographic separation. The performed quantum chemical calculation have shown that protonated pseudoephedrine contains stronger hydrogen bond than protonated ephedrine, which can justify the observed higher relative abundance of ion [M+H–H2O]+ in the mass spectrum of pseudoephedrine, in comparison to that of ephedrine.

First drug-checking study at an electronic festival and fentanyl detection in the central region of Mexico

BackgroundPerception of drug adulteration has increased in Mexico, but there is little research on adulterants and toxicity. The aim of this study was to identify drug composition in an electronic music outdoor festival nearby Mexico City.MethodsThe participants completed a questionnaire with demographic data, harm reduction strategies, drug-use patterns, history, and the drug they expected to find. We took a small sample of each substance and prepared it for drug checking. A two-section drug testing station was placed within the grounds of the festival. Interaction with participants occurred at the front part. Drug checking was conducted at the rear part. The service was free of charge, voluntary and confidential. Forty persons aged 22 to 48 years participated (mode = 28), of which 92.5% were male, most (82.5%) were single. Through the Substance Analysis Program of “ReverdeSer Collective,” we conducted the testing with the attendants that provided 51 drug samples, following ethical and biosafety protocols. We used colorimetry, Fourier Transform Infrared Spectroscopy, and fentanyl immunoassay strips for sample analysis.ResultsSubstances of choice among attendants were psychostimulants (MDMA and other amphetamine-like drugs) and hallucinogens. Most samples contained what the users expected plus adulterants. Main adulterants were methylene-dioxy-ethyl-amphetamine, methylene-dioxy-propyl-amphetamine, hydroxyamphetamine, and the selective serotonin reuptake inhibitor venlafaxine. Fentanyl was present in 2 out of 4 cocaine samples and in 14 of the 22 confirmed MDMA samples.ConclusionsSome of the adulterants found pose serious health risks, especially fentanyl, amphetamine-like substances, and venlafaxine. Therefore, it is urgent to monitor these adulterants at electronic music festivals and to implement prevention, treatment, and harm reduction public policies. Naloxone distribution and drug-assisted therapies should be part of government programs in Mexico.

New β-arylchalcogeno amines with procognitive properties targeting Carbonic Anhydrases and Monoamine Oxidases

Cognitive deficits are enduring and disabling symptoms for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. In this study, we reported the synthesis of β-arylchalcogeno amines bearing sulfurated, selenated, and tellurated moieties (2–4) which are structurally related to amphetamine with good activation properties for Carbonic Anhydrases (CAs) isoforms present in the cortical and hippocampal brain structures (hCA IV and hCA XIV). In addition, these compounds showed selective inhibition against the Monoamine oxidase (MAO) A isoform. In vivo evaluation of two derivatives (2a and 3a) revealed procognitive effects in the object recognition and social discrimination tests. Interestingly, these compounds, despite having a similar structure to amphetamine, did not caused hypophagia or hyperlocomotion, two effects often observed following the administration of amphetamine-like drugs. In this context, β-arylchalcogeno amines may have utility for improving the symptoms of cognitive decline associated with neurodegenerative and psychiatric diseases such as attention deficit disorder, Parkinson's disease-related cognitive dysfunction and cognitive disorders associated with depression.

Brief history of the medical and non-medical use of amphetamine-like psychostimulants

The alkaloid ephedrine derived from Ephedra vulgaris is at the origin of psychostimulant-drugs as amphetamine. These drugs have been principally utilized for medical treatments in the past, while their utilization has been largely reduced from the 1970s when the high risk of addiction and abuse has been recognized. The first reported treatments were as anti-asthmatics and to contrast narcolepsy until their recreational stimulant and anorexic effects were reported. Benzedrine and Pervitin use were of great importance during the Second World War due to their abundant utilization among military troops. Nowadays the use of selective amphetamine-like drugs is limited to ADHD treatment.

Syntheses and analytical characterizations of novel (2-aminopropyl)benzo[b]thiophene (APBT) based stimulants.

Two groups of amphetamine-like drugs with psychostimulant properties that were first developed during the course of scientific studies and later emerged as new psychoactive substances (NPS) are based on the (2-aminopropyl)indole (API) and (2-aminopropyl)benzofuran (APB) structural scaffolds. However, sulfur-based analogs with a benzo[b]thiophene structure (resulting in (2-aminopropyl)benzo[b]thiophene (APBT) derivatives) have received little attention. In the present investigation, all six racemic APBT positional isomers were synthesized in an effort to understand their structure-activity relationships relative to API- and APB-based drugs. One lesson learned from the NPS phenomenon is that one cannot exclude the appearance of such substances on the market. Therefore, an in-depth analytical characterization was performed, including various single- and tandem mass spectrometry (MS) and ionization platforms coupled to gas chromatography (GC) and liquid chromatography (LC), nuclear magnetic resonance spectroscopy (NMR), and solid phase and GC condensed phase infrared spectroscopy (GC-sIR). Various derivatizations have also been explored; it was found that all six APBT isomers could be differentiated during GC analysis after derivatization with heptafluorobutyric anhydride and ethyl chloroformate (or heptafluorobutyric anhydride and acetic anhydride) under non-routine conditions. Discriminating analytical features can also be derived from NMR, GC-EI/CI- single- and tandem mass spectrometry, LC (pentafluorophenyl stationary phase), and various infrared spectroscopy approaches (including GC-sIR). Availability of detailed analytical data obtained from these novel APBT-type stimulants may be useful to researchers and scientists in cases where forensic and clinical investigations are warranted.

Fatal \u03b1-PVP and amphetamine poisoning during a sauna and autoerotic practices

We describe the sudden death of a middle-aged man while having a sauna under the influence of α-pyrrolidinovalerophenone (α-PVP) (PM blood concentration: 0.8 mg/L), amphetamine (0.34 mg/L), and other drugs (buprenorphine, benzodiazepines), and engaging in solitary sexual activities. The drugs’ effects on the cardio-circulatory system and on body thermoregulation combined with the high temperatures are likely to have been central mechanisms leading to death. The high levels of adrenaline triggered by sexual arousal and the respiratory depression caused by buprenorphine, in association with benzodiazepines, may have also contributed to his death. This previously unreported type of accidental autoerotic death illustrates the risk of using amphetamine-like sympathomimetic drugs (e.g. cathinone derivates) in hot environments such as a sauna, and during sexual activities therein.

Stabilization of formaldehyde into polydimethylsiloxane composite: application to the in situ determination of illicit drugs.

The Marquis test is the most frequently used spot color assay for the screening of unknown drugs such as amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-metilenedioxymethamphetamine, and morphine. However, this test involves the use of the toxic reagent formaldehyde, as well as the manipulation of concentrated sulfuric acid. Here, we report a new format of this test that improves the sustainability and safety for the operator by immobilizing formaldehyde into a polydimetylsiloxane composite. In contact with a solution (or suspension) of the suspected sample in sulfuric acid, the dispositive delivers formaldehyde and the reaction takes place in a few seconds. Under the proposed conditions, only small amounts of the drug (μg) are necessary to produce intense changes of color. In addition, the percentage of the drug in the sample can be established by obtaining pictures of the test vials and subsequent analysis of the digitalized images. The responses were linear for amphetamine-like drugs up to a concentration of 100mgL-1, and the precision achieved was adequate (relative standard deviations, RSDs < 10%). The developed composites were tested for the determination of MDMA in several drug street samples, and a good correlation with the results obtained by a reference method based on liquid chromatography was found. The main advantages of the proposed approach over the traditional Marquis test format are better portability and safety for the operator at a lower cost and the possibility of using it for quantitative analysis.

3,4-Methylenedioxymethamphetamine, mephedrone, and β-phenylethylamine release dopamine from the cytoplasm by means of transporters and keep the concentration high and constant by blocking reuptake

The addiction-related behavioural effects of drugs of abuse are mediated by the mesocorticolimbic monoamine systems. We investigated the effects of 3,4-methylenedioxymethamphetamine (MDMA), mephedrone, β-phenylethylamine (β-PEA) methylphenidate (MPH) on dopamine release from mouse perfused nucleus accumbens and prefrontal cortex slices. The fractional release of [3H]-dopamine was measured at rest and in response to field stimulation. The distributions of [3H]-dopamine and its metabolites were determined using high-pressure liquid chromatography. The effect of drugs on [3H]-dopamine uptake was measured in synaptosomal P2 preparations from the frontal cortex and striatum. Similar to MDMA, mephedrone β-PEA increased the resting release of [3H]-dopamine from the nucleus accumbens and prefrontal cortex in a [Ca2+]o-independent manner, and the stimulation-evoked release was also augmented. In contrast, MPH failed to affect the resting release but potentiated the release in response to axonal activity. Similar to dopamine transporter antagonist GBR 12909, mephedrone, MDMA and MPH biphasically inhibited the [3H]-dopamine uptake. The administration of GBR 12909 and nisoxetine, or lowering the bath temperature prevented MDMA, mephedrone and β-PEA from enhancing the resting, cytoplasmic release of [3H]-dopamine, indicating the role of transporters in the release process. We conclude that amphetamine-like drugs of abuse and the trace amine β-PEA excessively increase the [Ca2+]o-independent, non-vesicular release of dopamine from the cytoplasm into the extrasynaptic space and inhibit the high-affinity transporters, thereby maintaining a high ambient, non-synaptic concentration of dopamine that may tonically control the activity of neurons equipped with dopamine receptors and is likely involved in the reinforcing effects and abusive potential of amphetamines.

Lack of Detection of New Amphetamine-Like Drugs Using Conventional Urinary Immunoassays.

The number of reports of serious adverse effects and intoxication after the use of the new drug 4-fluoroamphetamine (4-FA) increases. At the Emergency Department of the OLVG-Oost Hospital in Amsterdam, an on-site drug test, the Triage TOX Drug Screen, is available to assist in a rapid diagnosis. In less urgent cases, an EMIT II Plus immunoassay is used to determine semiquantitatively the presence of drugs of abuse (DOA). The antibodies in these immunoassays are designed to detect classic DOA and its urinary metabolites. Amphetamine-like drugs that may cause serious toxicity or impairment may not cross-react with the available immunoassay kits, and therefore may stay undetected. The question arises as to whether 4-FA and paramethoxymethamphetamine (PMMA) are detectable in the toxicological screening procedures commonly used for testing in urine. Synthetic urine was spiked with the drug under investigation to create spiking standards of 50, 100, 250, 500, 2500, and 5000 ng/mL. Urine drug screens were performed on the automated analyzer Biosite Triage MeterPro using the Triage TOX Drug Screen test and on a Siemens Drug Testing System Viva-E using the EMIT II Plus Ecstasy Assay and the EMIT II Plus Amphetamines Assay. In this concentration range, the EMIT II Plus did not screen positive for PMMA, but there was some cross-reactivity for PMMA on the EMIT II Plus Ecstasy assay. The Triage TOX Drug Screen did test positive for PMMA at a concentration of 2500 ng/mL. The EMIT II Plus Amphetamines did test positive for 4-FA at a concentration of 5000 ng/mL, whereas the Ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] assay only showed low cross-reactivity for 4-FA. The Triage TOX Drug Screen did not test positive for 4-FA. The available immunoassays lack sensitivity to detect 4-FA and PMMA in lower urine concentrations. Awareness of the fact that novel DOA may lead to false-negative urinary drug tests is of great importance.

Fenethylline (Captagon) abuse: Case report and literature review

IntroductionNovel psychoactive drugs (NPS) has rapidly increase in the last years in the drug market as a recreational use. Fenethylline is a theophylline, an amphetamine-like drug, having stimulant effects similar to those of other amphetamine-type derivatives. Fenethylline was used as medicament for hyperactivity disorders in children, narcolepsy and depression, but it has also been used as a drug of abuse under the common name of ‘captagon’. The purpose of this report is to review the clinical evidence for the potential of abuse of fenethylline. We propose a case report and literature review.MethodWe conducted a systematic review of the literature with the principal database (PubMed, Enbase, PsychInfo) and we present a case report.ResultsThe effects of fenethylline is characterized by euphoria, derealization, autopsychic and somatopsychic depersonalization, hallucination, agitation and decrease of pain perception.Discussion and conclusionThe primary drug market for fenethyline (as captagon) has traditionally been countries located on the Arabian Peninsula but also North Africa since 2013. To our knowledge, there is no report on the recreational use of fenethylline in literature. The clinical features of fenethylline intoxication were also similar to effects from other amphetamine-like drugs. In our case report, dissociative symptoms are the core of fenethylline intoxication. Further research is warranted to replicate our clinical and qualitative observations and, in general, quantitative studies in large samples followed-up over time are needed. Methodological limitations, clinical implications and suggestions for future research directions are considered [1,2].Disclosure of interestThe authors have not supplied their declaration of competing interest.

A solid colorimetric sensor for the analysis of amphetamine-like street samples

A solid sensor obtained by embedding 1,2-naphthoquinone-4-sulfonate (NQS) into polydimethylsiloxane/tetraethylortosilicate/silicon dioxide nanoparticles composite has been developed to identify and determine amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxymetamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA). The analytes are derivatized inside the composite for 10 min to create a colored product which can be then quantified by measuring the diffuse reflectance or the color intensity after processing the digitalized image. Satisfactory limits of detection (0.002–0.005 g mL−1) and relative standard deviations (<10%) have been achieved. The proposed kit has been successfully validated and applied to the analysis of amphetamine-like drugs street samples. The kit allows the in-situ screening of the mentioned illicit drugs owing to its simplicity, rapidity and portability, with excellent sensor stability and at a very low-cost.

3,4-methylenedioxypyrovalerone (MDPV) Induces Cytotoxic Effects on Human Dopaminergic SH-SY5Y Cells

Background. Synthetic cathinones are a rapidly growing group of psychostimulant drugs usually referred to as bath salts and have been used as an alternative to classic amphetamine-like drugs, with 3,4-methylenedioxypyrovalerone (MDPV) being one of the most prevalent constituents. Consistent with the effects of other psychostimulants, MDPV may induce neurotoxicity by altering monoamine systems in the brain or by inducing neuronal apoptosis. Purpose. The aim of this study was to evaluate the effects of MDPV on the human dopaminergic cell line SH-SY5Y. Experimental design. After 24-hour exposure to MDPV (100µ Mt o 2.5 mM), cytotoxicity, cellular proliferation, and apoptosis were evaluated, whereas reactive oxygen species (ROS) production was evaluated at 2 h, 4 h, 6 h, 22 h, and 24 h. Results. MDPV increased ROS production after 1 h, 4 h, and 6 h of exposure in all but the highest concentration; a moderate increase was observed at 22 h and 24 h. Only high concentrations of the drug decreased cellular proliferation and induced apoptosis and necrosis. Conclusion. MDPV induces dopaminergic toxicity by decreasing cellular proliferation and by increasing apoptosis and necrosis. The production of ROS may play a role in the early response to the drug.

Las nuevas drogas: origen, mecanismos de acción y efectos. Una revisión de la literatura

Introducción: existen en el mercado sustancias psicoactivas de reciente aparición que se conocen genéricamente como nuevas drogas, drogas de diseño o drogas “legales”. Objetivo:esta revisión de la literatura presenta las principales características de estos compuestos, los efectos que producen y lo que se conoce acerca de sus mecanismos de acción con la intención de informar a clínicos e investigadores en el campo de las adicciones. Método: búsqueda de la literatura sobre el desarrollo, los mecanismos de acción, los efectos clínicos y el mercado de las catinonas, los cannabinoides sintéticos y el krokodil. Resultados: se estima que hay más de 450 sustancias de este tipo, la mayoría de las cuales son estimulantes tipo anfetamínicos, en particular, catinonas sintéticas (conocidas como “sales de baño”) o cannabinoides sintéticos que se venden como “mezclas herbales” o “aromatizantes ambientales”; también hay algunos opioides y alucinógenos. Estas sustancias tienen en común que evaden sistemas de regulación, son difíciles de detectar, se venden como alternativas “legales” a drogas conocidas, compuestos de investigación o suplementos alimenticios. Las fuentes para su vigilancia epidemiológica son, entre otras, datos obtenidos de servicios de emergencia y decomisos en diferentes países del mundo. Las estrategias de comercialización de estos productos incluyen la venta en envases marcados con la leyenda “no apto para consumo humano”, con el propósito de evadir sistemas de control sanitarios. Se venden en pequeños comercios y a través de medios electrónicos. Discusión y conclusiones: no hay suficiente investigación acerca de sus efectos pero, cuando existe, demuestra que son dañinos y con alto potencial adictivo.

Stereochemistry of mephedrone neuropharmacology: enantiomer-specific behavioural and neurochemical effects in rats.

Synthetic cathinones, commonly referred to as 'bath salts', are a group of amphetamine-like drugs gaining popularity worldwide. 4-Methylmethcathinone (mephedrone, MEPH) is the most commonly abused synthetic cathinone in the UK, and exerts its effects by acting as a substrate-type releaser at monoamine transporters. Similar to other cathinone-related compounds, MEPH has a chiral centre and exists stably as two enantiomers: R-mephedrone (R-MEPH) and S-mephedrone (S-MEPH). Here, we provide the first investigation into the neurochemical and behavioural effects of R-MEPH and S-MEPH. We analysed both enantiomers in rat brain synaptosome neurotransmitter release assays and also investigated their effects on locomotor activity (e.g. ambulatory activity and repetitive movements), behavioural sensitization and reward. Both enantiomers displayed similar potency as substrates (i.e. releasers) at dopamine transporters, but R-MEPH was much less potent than S-MEPH as a substrate at 5-HT transporters. Locomotor activity was evaluated in acute and repeated administration paradigms, with R-MEPH producing greater repetitive movements than S-MEPH across multiple doses. After repeated drug exposure, only R-MEPH produced sensitization of repetitive movements. R-MEPH produced a conditioned place preference whereas S-MEPH did not. Lastly, R-MEPH and S-MEPH produced biphasic profiles in an assay of intracranial self-stimulation (ICSS), but R-MEPH produced greater ICSS facilitation than S-MEPH. Our data are the first to demonstrate stereospecific effects of MEPH enantiomers and suggest that the predominant dopaminergic actions of R-MEPH (i.e. the lack of serotonergic actions) render this stereoisomer more stimulant-like when compared with S-MEPH. This hypothesis warrants further study.

First detection of ethylphenidate in human fatalities after ethylphenidate intake

Methylphenidate, a psychostimulant drug from the group of amphetamines is, among others, established in the treatment of attention deficit hyperactivity disorder and narcolepsy. It is also known to have a certain potential of abuse. In combination with alcohol, the metabolite ethylphenidate was detected in human plasma in small amounts. However, ethylphenidate is sold as “research chemical” via the Internet. It was put under German narcotics law in July 2013. In a recent case, where a deceased person was found in his apartment, the police seized a plastic bag with the inscription “ethylphenidate”. An autopsy of the 32-year-old man yielded a mitral valve endocarditis, which must have persisted a while before death, in combination with a pneumonia.At the Forensic Toxicological Centre (FTC) in Munich femoral blood, liver, pericardium fluid, urine, stomach content and hair of the deceased were analyzed for ethylphenidate after sample preparation by an LC-Triple TOF 5600. Calibration curves were spiked with a methanolic 1mg/mL solution of ethylphenidate (substance provided by the State Office of Criminal Investigation in Munich) in whole blood in comparison to liver and femoral blood, in serum in comparison to pericardium fluid and in urine in comparison to urine and stomach content, respectively.Ethylphenidate was detected in all analyzed matrices. The spectrums of the human specimen were compared to those obtained from the calibration curves and identified as ethylphenidate. The measured concentrations were for femoral blood 110ng/mL, for liver 180ng/g, for pericardium fluid 131ng/mL, for urine 987ng/mL and for stomach content 20.7ng/mL, respectively. The stomach contained 200mL of a brownish-coloured liquid, resulting in a total amount of 4000ng ethylphenidate. The lowest calibrator for whole blood and serum was 1ng/mL and for urine 10ng/mL.As far as it is known to the authors, these are the first ethylphenidate levels measured in a case of ethylphenidate intake. Therefore these results can only be compared to methylphenidate concentrations with therapeutic levels ranging from 5 to 60ng/mL in serum. As the toxic levels for methylphenidate start from approximately 500ng/mL serum, we estimate that ethylphenidate in the concentrations mentioned above is not in a directly lethal range. But it has to be considered, that amphetamine-like drugs as methylphenidate are known for their cardiovascular side effects (like tachycardia and arrhythmia) and might therefore have contributed to death, which was attributed to endocarditis in combination with pneumonia.

Using cheminformatics to predict cross reactivity of "designer drugs" to their currently available immunoassays.

BackgroundA challenge for drug of abuse testing is presented by ‘designer drugs’, compounds typically discovered by modifications of existing clinical drug classes such as amphetamines and cannabinoids. Drug of abuse screening immunoassays directed at amphetamine or methamphetamine only detect a small subset of designer amphetamine-like drugs, and those immunoassays designed for tetrahydrocannabinol metabolites generally do not cross-react with synthetic cannabinoids lacking the classic cannabinoid chemical backbone. This suggests complexity in understanding how to detect and identify whether a patient has taken a molecule of one class or another, impacting clinical care.MethodsCross-reactivity data from immunoassays specifically targeting designer amphetamine-like and synthetic cannabinoid drugs was collected from multiple published sources, and virtual chemical libraries for molecular similarity analysis were built. The virtual library for synthetic cannabinoid analysis contained a total of 169 structures, while the virtual library for amphetamine-type stimulants contained 288 compounds. Two-dimensional (2D) similarity for each test compound was compared to the target molecule of the immunoassay undergoing analysis.Results2D similarity differentiated between cross-reactive and non-cross-reactive compounds for immunoassays targeting mephedrone/methcathinone, 3,4-methylenedioxypyrovalerone, benzylpiperazine, mephentermine, and synthetic cannabinoids.ConclusionsIn this study, we applied 2D molecular similarity analysis to the designer amphetamine-type stimulants and synthetic cannabinoids. Similarity calculations can be used to more efficiently decide which drugs and metabolites should be tested in cross-reactivity studies, as well as to design experiments and potentially predict antigens that would lead to immunoassays with cross reactivity for a broader array of designer drugs.

Methylphenidate Poisoning: Carpopedal Spasm in a Child

Stimulant drugs including methylphenidate (MPH) are the first-line treatment for school-aged children and adolescents with attention-deficit hyperactivity disorder (ADHD). Since its availability, MPH overdoses have been seen more commonly similar to overdoses with other amphetamine-like drugs. Although the clinical manifestations include symphathomimetic findings like irritability, agitation, palpitation, hyperreflexia, seizures, hypertension, hyperventilation and hyperthermia, it may also cause stroke, tics, toxic psychosis, Tourette’s syndrome and neuromuscular findings such as dyskinesia and paresthesia. Carpopedal spasm is a rare feature of MPH overdose. It may be triggered by alkalosis-induced hypocalcamia or cerebral vasoconstriction associated with hypocapnia. In this case report, we presented a 10-year-old girl who had carpopedal spasm after 3 - 4 h from taking the MPH with high dosage. Paper bag ventilation as the treatment had a significant improving effect on carpopedal spasm. J Med Cases. 2014;5(1):31-33 doi: http://dx.doi.org/10.4021/ jmc1616w

Neuronal Mitochondrial Trafficking Impairment: The Cause or a Consequence of Neuronal Dysfunction Caused by Amphetamine-Like Drugs

Drugs of abuse cause a variety of complex neuronal events at the cellular level, including changes in membrane excitability and neurotransmission, activation of complex signaling pathways, altered synaptic physiology and structural changes, and drug-evoked synaptic plasticity and neurotoxicity, which mediate both acuteand long-lasting effects and addiction. Neuronal mitochondria are highly dynamic organelles that, by undergoing fusion and fission events, are efficiently translocated along the neuronal processes, frequently changing direction, pausing or switching to persistent docking. The neuronal integrity and functionality are dependent upon the proper maintenance of a healthy mitochondrial population and their efficient distribution. There is a general consensus that mitochondrial-dependent pathways can provide a major understanding concerning pathological processes underlying neurotoxicity of drugs of abuse. As such, it is plausible to consider that alterations on mitochondrial trafficking may be key players on the neuronal effects mediated by these drugs. This work aims to provide a comprehensive and up-to-date review of the data linking mitochondrial trafficking impairment to amphetamine-like drugs, and, thus, contribute to a better understanding of their neuronal effects. Additionally, new research data describing alterations in neuronal mitochondrial trafficking for 3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) conjugated metabolites 5-(glutathion-S-yl)-N-methyl-α-methyldopamine [5-(GSH)-N-Me-α-MeDA] and 5-(N-acetylcystein-S-yl)-N-methyl-α- methyldopamine [5-(NAC)-N-Me-α-MeDA] are also provided.

Methylphenidate Poisoning: Carpopedal Spasm in a Child

Stimulant drugs including methylphenidate (MPH) are the first-line treatment for school-aged children and adolescents with attention-deficit hyperactivity disorder (ADHD). Since its availability, MPH overdoses have been seen more commonly similar to overdoses with other amphetamine-like drugs. Although the clinical manifestations include symphathomimetic findings like irritability, agitation, palpitation, hyperreflexia, seizures, hypertension, hyperventilation and hyperthermia, it may also cause stroke, tics, toxic psychosis, Tourette’s syndrome and neuromuscular findings such as dyskinesia and paresthesia. Carpopedal spasm is a rare feature of MPH overdose. It may be triggered by alkalosis-induced hypocalcamia or cerebral vasoconstriction associated with hypocapnia. In this case report, we presented a 10-year-old girl who had carpopedal spasm after 3 - 4 h from taking the MPH with high dosage. Paper bag ventilation as the treatment had a significant improving effect on carpopedal spasm. J Med Cases. 2014;5(1):31-33 doi: https://doi.org/10.4021/jmc1616w