Article
Biochemistry & Molecular Biology
Olga Wronikowska-Denysiuk, Agnieszka Michalak, Anna Pankowska, Lukasz Kurach, Paulina Koziol, Artur Lazorczyk, Katarzyna Kochalska, Katarzyna Targowska-Duda, Anna Boguszewska-Czubara, Barbara Budzynska
Summary: The aim of this study was to assess the role of the GABA-ergic system in the rewarding effects of mephedrone. The results showed that GS39783, a positive allosteric modulator of GABA(B) receptors, blocked mephedrone-induced conditioned place preference (CPP), while baclofen, a GABA(B) receptor agonist, did not. Chromatographic analysis confirmed the behavioral effect, revealing a decrease in GABA hippocampal concentration following mephedrone administration. This study provides new insight into the involvement of the GABA-ergic system in the rewarding effects of mephedrone and suggests the potential of GABA(B) receptors as new targets for the pharmacological management of mephedrone use disorder.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Tetyana P. Buzhdygan, Cassidy R. Rodrigues, Hannah M. McGary, Jana A. Khan, Allison M. Andrews, Scott M. Rawls, Servio H. Ramirez
Summary: The study found that synthetic cathinones such as mephedrone can damage human brain endothelial cells, leading to disruption of the blood-brain barrier and endothelial dysfunction. Changes in key proteins resulted in increased permeability and decreased transendothelial resistance of the endothelial barrier, along with endothelial activation and inflammation.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Pharmacology & Pharmacy
Lourdes Poyatos, Clara Perez-Mana, Olga Hladun, Melani Nunez-Montero, Georgina de la Rosa, Soraya Martin, Ana Maria Barriocanal, Lydia Carabias, Benjamin Kelmendi, Omayema Taoussi, Francesco Paolo Busardo, Francina Fonseca, Marta Torrens, Simona Pichini, Magi Farre, Esther Papaseit
Summary: This study aimed to compare the pharmacological effects and abuse potential of synthetic stimulant Methylone with MDMA. The results showed that Methylone significantly increased blood pressure and heart rate and induced pleasurable effects such as stimulation, euphoria, wellbeing, enhanced empathy, and altered perception. The abuse potential of Methylone was comparable to that of MDMA in humans.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Marco Niello, Daniela Cintulova, Philip Raithmayr, Marion Holy, Kathrin Jaentsch, Claire Colas, Gerhard F. Ecker, Harald H. Sitte, Marko D. Mihovilovic
Summary: The study identified differences in activity of mephedrone and its metabolites at monoamine transporters, with enantioselectivity present at SERT. Two previously uncharacterized metabolites were discovered in a urine sample from a mephedrone user.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
F. Ivy Carroll, Anita H. Lewin, S. Wayne Mascarella, Herbert H. Seltzman, P. Anantha Reddy
Summary: The review discusses the exponential increase in clandestine manufacture of new psychoactive substances designed to circumvent regulations, which has led to a rise in fatalities. It focuses on three compound classes and highlights the medicinal chemistry approaches used by clandestine laboratories to develop new substances, as well as the chemical methods for treating illicit drug abuse.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2021)
Article
Psychiatry
Gniewko Wieckiewicz, Iga Stoklosa, Maciej Stoklosa, Wlodzimierz Wieckiewicz, Piotr Gorczyca, Tomasz M. Gondek
Summary: ADHD is considered a neurodevelopmental disorder that was thought to primarily affect children and diminish with age, but it is now known that symptoms can persist into adulthood for over 50% of patients. Many undiagnosed individuals turn to psychoactive substances to alleviate symptoms and improve their quality of life.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Nuria Nadal-Gratacos, Esther Lleixa, Monica Gibert-Serramia, Roger Estrada-Tejedor, Xavier Berzosa, Xavier Batllori, David Pubill, Jordi Camarasa, Elena Escubedo, Raul Lopez-Arnau
Summary: Changes in the molecular structure of synthetic cathinones have led to an increase in the number of novel emerging drugs in the illicit drug market. This study investigates the effects of para- and meta-halogen substitutions on the in vivo, in vitro, and in silico effects of alpha-PVP derivatives. The study provides evidence of the rewarding and anxiety-like properties of halogenated alpha-PVP derivatives.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Esther Papaseit, Eulalia Olesti, Clara Perez-Mana, Marta Torrens, Francina Fonseca, Marc Grifell, Mireia Ventura, Rafael de la Torre, Magi Farre
Summary: The study compared the acute pharmacological effects and saliva concentrations of mephedrone after oral and intranasal self-administration. Results showed that intranasal self-administration led to significantly higher concentrations, but oral route sometimes produced greater effects.
Article
Pharmacology & Pharmacy
Courtney Gearlds, Jessica Brooke Bouldin, Mariah McKinney, Shannon Schreiner, Stacy D. Brown, Brooks B. Pond
Summary: This study investigated the pharmacokinetic interactions of synthetic cathinones MDPV, mephedrone, and methylone when used in combination. Results showed altered drug concentrations and total drug exposure, providing insight into the consequences of co-exposure to these substances in popular bath salt products.
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
(2021)
Article
Biochemistry & Molecular Biology
Elisabet Teixido, Clara Riera-Colomer, Demetrio Raldua, David Pubill, Elena Escubedo, Marta Barenys, Raul Lopez-Arnau
Summary: This study evaluates the cardiovascular toxicity of synthetic cathinones and traditional psychostimulants in zebrafish embryos. The results show that all drugs can induce bradycardia, arrhythmia, and atrial-ventricular block, with MDPV being the most potent in inducing these effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Marco Niello, Spyridon Sideromenos, Ralph Gradisch, Ronan O'Shea, Jakob Schwazer, Julian Maier, Nina Kastner, Walter Sandtner, Kathrin Jantsch, Carl R. Lupica, Alexander F. Hoffman, Gert Lubec, Claus J. Loland, Thomas Stockner, Daniela D. Pollak, Michael H. Baumann, Harald H. Sitte
Summary: By using various in vitro, computational, and in vivo approaches, we found that the drug-binding kinetics of S-enantiomers of pyrovalerone analogs at DAT correlate with the time-course of in vivo psychostimulant action in mice. In particular, the slow dissociation (i.e., slow koff) of S-enantiomers of pyrovalerone analogs from DAT can predict their more persistent in vivo effects compared to cocaine and methylphenidate. Overall, our findings highlight the critical importance of drug-binding kinetics at DAT in determining the in vivo profile of effects produced by psychostimulant drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Lourdes Poyatos, Esther Papaseit, Eulalia Olesti, Clara Perez-Mana, Mireia Ventura, Xoan Carbon, Marc Grifell, Francina Fonseca, Marta Torrens, Rafael de la Torre, Magi Farre
Summary: Methylone, a synthetic cathinone considered the beta-keto analogue of MDMA, is commonly used as a substitute for traditional psychostimulants. Limited data is available on its pharmacology, but observational studies have shown that its effects are similar to MDMA but less intense, with oral fluid concentrations serving as a suitable biomarker for acute exposure.
Article
Medicine, Legal
Flaminia Vincenti, Adolfo Gregori, Martina Flammini, Fabiana Di Rosa, Alberto Salomone
Summary: The availability and consumption of NPS have increased rapidly, posing risks to public health and challenging law enforcement efforts. Through analysis using GC-MS and HPLC-HRMS, synthetic cathinones were identified as the most prevalent compounds in NPS on the Italian territory.
FORENSIC SCIENCE INTERNATIONAL
(2021)
Article
Electrochemistry
Mariane O. B. Arrieiro, Luciano C. Arantes, Debora A. R. Moreira, Dilton M. Pimentel, Camila D. Lima, Livia M. F. Costa, Rodrigo M. Verly, Wallans T. P. dos Santos
Summary: This study presents the electrochemical detection of the synthetic cathinone eutylone for the first time. The electrochemical behavior of eutylone was investigated using glassy carbon and carbon graphite electrodes. The proposed method exhibited good stability and selectivity for eutylone detection in seized samples.
ELECTROCHIMICA ACTA
(2022)
Review
Neurosciences
Fabrizio Schifano, Stefania Chiappini, Andrea Miuli, John Martin Corkery, Norbert Scherbaum, Flavia Napoletano, Davide Arillotta, Caroline Zangani, Valeria Catalani, Alessandro Vento, Mauro Pettorruso, Giovanni Martinotti, Di Giannantonio Massimo, Amira Guirguis
Summary: The use of several new psychoactive substances (NPS) has become popular, posing global health risks. This systematic review investigated the association between Serotonin Syndrome (SS) and NPS intake, finding that various NPS can lead to SS, including psychedelic phenethylamines and synthetic cathinones. Most substances were ingested orally, but other routes were reported. A majority of subjects had no psychiatric history.
EXPERIMENTAL NEUROLOGY
(2021)
Correction
Critical Care Medicine
Anahita Rouze, Ignacio Martin-Loeches, Pedro Povoa, Demosthenes Makris, Antonio Artigas, Mathilde Bouchereau, Fabien Lambiotte, Matthieu Metzelard, Pierre Cuchet, Claire Boulle Geronimi, Marie Labruyere, Fabienne Tamion, Martine Nyunga, Charles-Edouard Luyt, Julien Labreuche, Olivier Pouly, Justine Bardin, Anastasia Saade, Pierre Asfar, Jean-Luc Baudel, Alexandra Beurton, Denis Garot, Iliana Ioannidou, Louis Kreitmann, Jean-Francois Llitjos, Eleni Magira, Bruno Megarbane, David Meguerditchian, Edgar Moglia, Armand Mekontso-Dessap, Jean Reignier, Matthieu Turpin, Alexandre Pierre, Gaetan Plantefeve, Christophe Vinsonneau, Pierre-Edouard Floch, Nicolas Weiss, Adrian Ceccato, Antoni Torres, Alain Duhamel, Saad Nseir
INTENSIVE CARE MEDICINE
(2022)
Article
Critical Care Medicine
Philippe Nguyen, Lucie Chevillard, Ahmed S. Gouda, Herve Gourlain, Laurence Labat, Isabelle Malissin, Nicolas Deye, Sebastian Voicu, Bruno Megarbane
Summary: The study evaluated the effects of L-carnitine on the treatment of acute valproic acid poisoning, showing that L-carnitine did not significantly enhance valproic acid clearance. However, its impact on accelerating blood lactate level normalization and preventing organ dysfunction remained uncertain. Investigation into valproic acid toxicokinetics and concentration/effect relationships may aid in improving patient management.
ANNALS OF INTENSIVE CARE
(2022)
Review
Pharmacology & Pharmacy
Sebastian Voicu, Aymen M'Rad, Isabelle Malissin, Nicolas Deye, Bruno Megarbane
Summary: This article provides a review of the indications, timing, and outcomes of extracorporeal life support (ECLS) in the treatment of cardiotoxicant-poisoned patients. Despite limited evidence, ECLS appears to improve survival in selected patients. Further clarification of selection criteria is necessary.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Clinical Neurology
Luisa Alessandra Atehortua Martinez, Emmanuel Curis, Nawel Mekdad, Claire Larrieu, Cindie Courtin, Laurent Jourdren, Corinne Blugeon, Jean-Louis Laplanche, Bruno Megarbane, Cynthia Marie-Claire, Nadia Benturquia
Summary: The study investigated the variability in the expression of the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm and identified differentially expressed genes in the nucleus accumbens (NAc) between rats that did or did not express cocaine-induced place preference. The findings provide insights into the mechanisms underlying interindividual variability in response to cocaine's rewarding effects, with immediate early genes showing differential expression in CPPE rats.
JOURNAL OF PSYCHOPHARMACOLOGY
(2022)
Article
Health Care Sciences & Services
Thomas Lacoste-Palasset, Laetitia Sutterlin, Aymen M'Rad, Louis Modestin, Vianney Mourman, Adrien Pepin-Lehalleur, Isabelle Malissin, Giulia Naim, Caroline Grant, Emmanuelle Guerin, Jean-Michel Ekherian, Nicolas Deye, Bruno Megarbane, Sebastian Voicu
Summary: In this single-center retrospective cohort study, early discussion of limitation of therapeutic effort (LTE) did not increase in-hospital mortality in elderly COVID-19 patients while reducing the use of organ support techniques.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Bruno Megarbane
Summary: High-dose insulin (HDI) therapy with adapted glucose supplementation is suggested as a first-line treatment for calcium-channel blocker (CCB) poisonings. Our narrative review supports the effectiveness and safety of HDI based on published experimental studies, case reports, and experts' opinions. HDI is strongly recommended in CCB-poisoned patients with cardiovascular compromise, especially if cardiac function impairment has been diagnosed, without delaying the administration of vasopressors/inotropic drugs.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Mathieu Klein, Vanessa Naffaa, Lucie Chevillard, Patricia Risede, Bruno Saubamea, Homa Adle-Biassette, Bruno Megarbane
Summary: Due to a narrow therapeutic index, prolonged lithium treatment and overdose may lead to reversible neurotoxicity. However, in rare severe poisonings, irreversible brain injuries have been reported. This study aimed to investigate the histopathological consequences of lithium exposure in rat models and found that no brain lesion or significant difference in neuron and astrocyte counts were observed between lithium-treated rats and controls, suggesting that lithium-induced neurotoxicity is reversible and brain injury is not a common feature of toxicity.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Editorial Material
Toxicology
Bruno Megarbane, Nawel Gharnaout, Nouzha Djebrani Oussedik
Summary: This article reports a case of misdiagnosis of body packing as a result of misinterpreting imaging results. A 55-year-old woman presented with uncontrolled vomiting in the airport transit area. Imaging showed multiple radiopaque foreign bodies in the colon, leading to the mistaken diagnosis. The final diagnosis was radiopaque pharmacobezoars caused by severe hypokalemia-associated paralytic ileus following post-chemotherapy vomiting.
CLINICAL TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Pascal Houze, Ilona Borowski, Eugenie Bito, Romain Magny, Athina Morcos, Sebastian Voicu, Bruno Megarbane, Laurence Labat
Summary: In toxicology, chromatographic methods coupled to HR/MS are commonly used for screenings, with the development of methods for alternative samples such as Volumetric Adsorptive Micro-Sampling. The optimized extraction procedure using Mitra (TM) allowed the confirmation of 87 compounds in spiked whole blood, with identification limits below 12.5 ng center dot mL(-1) for 82.2% of the investigated drugs. The novel screening approach showed a satisfying concordance in the analysis of poisoned patients' samples.
Article
Biochemistry & Molecular Biology
Romain Magny, Bruno Megarbane, Pauline Guillaud, Lucie Chevillard, Nicolas Auzeil, Pauline Thiebot, Sebastian Voicu, Isabelle Malissin, Nicolas Deye, Laurence Labat, Pascal Houze
Summary: Metabolomics in clinical toxicology aims to identify and semi-quantify a wide range of endogenous and exogenous metabolites. In this study, a three-step workflow was developed to investigate the metabolic impact of the antidepressant drug venlafaxine in a poisoned patient. Targeted quantitative and untargeted semi-quantitative metabolomic analyses were performed to determine the plasma kinetics of venlafaxine and its metabolites, and correlations between the metabolomic data and endogenous metabolites were explored. This preliminary study is a first step towards the application of toxicometabolomics in clinical toxicology and provides a useful workflow for identifying toxicity biomarkers.
Review
Chemistry, Medicinal
Karam Chamoun, Lucie Chevillard, Aline Hajj, Jacques Callebert, Bruno Megarbane
Summary: In 2020, fentanyl and its analogs accounted for around 65% of drug-related deaths in the USA, showing a concerning upward trend in the past decade. These synthetic opioids, originally intended for medical use, have been illegally diverted to recreational purposes. Unlike most opioids, fentanyl analogs can rapidly cause thoracic rigidity, increasing the risk of death. Further research is needed to better understand the mechanisms of neurorespiratory toxicity associated with fentanyl and its analogs, and to develop strategies to reduce fatalities.
Article
Psychology, Experimental
Clara De Groote, Olivier Cottencin, Philippe Tison, Claire Triquet, Jean-Louis Nandrino
Summary: The study investigated the relationship between autobiographical memories and individuals' self-conception in alcohol use disorder (AUD). AUD detoxified patients and control participants were asked to create a list of self-statements associated with autobiographical memories. The group variable was not linked to the number of positive self-statements, but it was associated with the number of negative self-statements. Additionally, the memories cued by positive self-statements were related to the group and the number of positive and general memories, while there was no association for the memories cued by negative self-statements. The use of adaptive emotional regulation strategies was the only significant predictor of the use of positive or negative self-statements in AUD patients.
Correction
Health Care Sciences & Services
Diane Friedman, Lamiae Grimaldi, Alain Cariou, Philippe Aegerter, Stephane Gaudry, Abdel Ben Salah, Haikel Oueslati, Bruno Megarbane, Nicolas Meunier-Beillard, Jean-Pierre Quenot, Carole Schwebel, Laurent Jacob, Segloene Robin Lagandre, Pierre Kalfon, Romain Sonneville, Shidasp Siami, Aurelien Mazeraud, Tarek Sharshar
JMIR RESEARCH PROTOCOLS
(2023)
Article
Pharmacology & Pharmacy
Giulia Naim, Isabelle Malissin, Bruno Megarbane
Summary: This study retrospectively reviewed cerebral magnetic resonance imaging (MRI) scans of poisoned patients from 2014 to 2021 and found that 4.7% of the patients had cerebral microbleeds. These microbleeds were mainly located in the white matter, possibly associated with prolonged hypoxemia. The direct relationship between toxicants and microbleeds is unclear, but physicians should be aware of this complication that may lead to sequelae.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Emergency Medicine
Mikael Laredo, Claire Vandiedonck, Oscar Miro, Juan Gonzalez del Castillo, Aitor Alquezar-Arbe, Javier Jacob, Pascual Pinera, Bruno Megarbane
Summary: This study compared the relationship between respiratory rate (RR) and peripheral oxygen saturation (SpO(2)) in patients with COVID-19 and those without COVID-19 on admission. The study found no difference in the RR/SpO(2) relationship between COVID-19 patients and non-COVID-19 patients, except among elderly patients.
EMERGENCY MEDICINE JOURNAL
(2023)