Article
Clinical Neurology
Karolina E. Kolaczynska, Paula Ducret, Daniel Trachsel, Marius C. Hoener, Matthias E. Liechti, Dino Luethi
Summary: This article examines the pharmacological properties of MDA analogs and related amphetamine-based compounds, including monoamine uptake inhibition and release, as well as transporter and receptor binding and activation properties. The study finds that some MDA analogs have similar pharmacological profiles to MDMA, while others have more pronounced dopaminergic activity. Further research on the pharmacokinetics and pharmacodynamics of these drugs is needed to better evaluate their risks and therapeutic potential.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Review
Psychiatry
David E. Nichols
Summary: At first glance, the molecular structures of MDMA and MDA seem similar, but their activity stereochemistry differs. MDMA is distinct from classical hallucinogenic phenethylamines in structure and psychopharmacology. It promotes affiliative social behavior, has acute anxiolytic effects, and induces introspection and personal reflection. Its mechanism of action involves the transport and release of neuronal serotonin.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Charlotte P. Magee, BaoMinh D. Le, Yasmeen H. Siripathane, Diana G. Wilkins, Glen R. Hanson, Annette E. Fleckenstein
Summary: MCAT induces changes in dopamine and serotonin transporter function in rat brain tissues, potentially involving calcium and protein kinase-C modulation.
JOURNAL OF NEUROCHEMISTRY
(2021)
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
Biochemistry & Molecular Biology
Karolina E. Kolaczynska, Jan Thomann, Marius C. Hoener, Matthias E. Liechti
Summary: Pyrovalerone cathinones are potent DAT and NET inhibitors with high selectivity, potentially leading to strong psychostimulant effects and high abuse liability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
L. Duart-Castells, N. Nadal-Gratacos, M. Muralter, B. Puster, X. Berzosa, R. Estrada-Tejedor, M. Niello, S. Bhat, D. Pubill, J. Camarasa, H. H. Sitte, E. Escubedo, R. Lopez-Arnau
Summary: The study highlights the role of amino terminal substitution in the pharmacological profile of novel synthetic cathinones, including their potency in inhibiting dopamine uptake and inducing psychostimulant and rewarding effects in mice. The results demonstrate a significant correlation between predicted binding affinities by molecular docking and affinity constants for human dopamine transporter, indicating the importance of amino substitutions in determining the biological activity of these compounds.
Article
Environmental Sciences
Wenxiu Liu, Heng Zhang, Yang Liu, Xu Li, Haijian Lu, Changsheng Guo, Jian Xu
Summary: This study investigated the occurrence, distribution, and ecological risks of psychoactive substances in the Qinghai-Tibet Plateau. The results showed relatively low contamination levels and ecological risks compared to other regions.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Article
Chemistry, Analytical
Camila Diana Lima, Larissa Magalhaes de Almeida Melo, Luciano Chaves Arantes, Nathalia dos Santos Conceicao, Izabela de Franca Schaffel, Lara Lima Machado, Rafael de Queiroz Ferreira, Wallans Torres Pio dos Santos
Summary: This study presents the electrochemical detection of 3',4'-Methylenedioxy-N-tert-butylcathinone (MDPT) using screen printed electrodes modified with carbon nanofibers. The proposed method showed high selectivity and stability for MDPT determination, making it a fast and simple screening method in forensic analysis.
Article
Biochemistry & Molecular Biology
Rachel A. Davies, Vy T. Nguyen, Jose M. Eltit, Richard A. Glennon
Summary: a-Pyrrolidinohexiophenone (a-PHP) is a synthetic cathinone central stimulant that is structurally similar to a-PVP. It is a potent dopamine transporter (DAT) reuptake inhibitor. In this study, a series of 4-substituted a-PHP analogues were examined, and most showed selective DAT reuptake inhibition with a narrow range of potency. The 4-CF3 analogue was an outlier with reduced potency and selectivity. QSAR study was not possible due to limited empirical results.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Jose A. Pino, Gabriel Nunez-Vivanco, Gabriela Hidalgo, Miguel Reyes Parada, Habibeh Khoshbouei, Gonzalo E. Torres
Summary: This study reveals that G protein beta gamma subunits can bind to the dopamine transporter (DAT) and activate DAT-mediated dopamine efflux, similar to the mechanism of action of psychostimulants like amphetamine (AMPH). Through a combination of computational biology, mutagenesis, biochemical, and functional assays, the amino acid residues within the 582-596 sequence of the DAT carboxy terminus involved in the DAT-G beta gamma interaction and G beta gamma-induced dopamine efflux were identified. Residues like R588 and F587 within the carboxy terminus of DAT play critical roles in the physical interaction between DAT and G beta gamma, influencing dopamine efflux.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemical Research Methods
Hannes Max Schwelm, Mattias Persson, Benedikt Pulver, Max Vincent Huss, Henrik Green, Volker Auwaerter
Summary: 1-(2,3-Dihydro-1H-inden-5-yl)-2-(piperidin-1-yl)pentan-1-one (3,4-Pr-PipVP), a new synthetic cathinone, was discovered in Germany in 2022. It was initially thought to contain a novel bicyclo[4.2.0]octatrienyl function but was later found to contain a scheduled indanyl ring. It is one of the few SCats with a piperidine ring and showed low potency as a blocker of monoamine transporters.
DRUG TESTING AND ANALYSIS
(2023)
Review
Neurosciences
Deborah Rudin, Matthias E. Liechti, Dino Luethi
Summary: New psychoactive stimulants and psychedelics still have a significant presence in the illicit new psychoactive substance market, with potential neurotoxic effects that may impact the brain's neurological system. However, the translation of preclinical data on NPS-induced neurotoxicity to humans remains uncertain.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Neurosciences
Vindhya Nawaratne, Sean P. McLaughlin, Felix P. Mayer, Zayna Gichi, Alyssa Mastriano, Lucia Carvelli
Summary: The dopamine 2 receptors (D2R) play an important role in mediating the effects of amphetamine, which primarily rely on the ability of amphetamine to increase extracellular dopamine. This study found that prolonged exposure to amphetamine can decrease or increase endogenous hD2R at the cellular membrane in HEK293 cells. Moreover, the effects of amphetamine on D2R expression may occur independently of dopamine and DAT.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
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)
Article
Biochemistry & Molecular Biology
Tao Ke, Ganesh Ambigapathy, Thanh Ton, Archana Dhasarathy, Lucia Carvelli
Summary: This study found that chronic embryonic exposure to amphetamine leads to changes in the expression of the DAT-1 gene in adult C. elegans, which is associated with an enhanced behavioral response to amphetamine in adult animals. Pharmacological and genetic interventions can prevent the long-lasting behavioral effects induced by amphetamine during embryogenesis. These findings are important for understanding how drugs of abuse can predispose to addiction, as the dopaminergic system and epigenetic mechanisms are highly conserved between C. elegans and mammals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Karolina E. Kolaczynska, Jan Thomann, Marius C. Hoener, Matthias E. Liechti
Summary: Pyrovalerone cathinones are potent DAT and NET inhibitors with high selectivity, potentially leading to strong psychostimulant effects and high abuse liability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Claudia Milazzo, Edwin J. Mientjes, Ilse Wallaard, Soren Vestergaard Rasmussen, Kamille Dumong Erichsen, Tejaswini Kakunuri, A. S. Elise van der Sman, Thomas Kremer, Meghan T. Miller, Marius C. Hoener, Ype Elgersma
Summary: Research findings demonstrate that ASO-induced reactivation of UBE3A in AS mice can lead to positive effects on AS phenotypes, such as restored sensitivity to seizures and improvements in behavior, indicating therapeutic potential.
Article
Biochemistry & Molecular Biology
David A. Barnes, Dylan A. Galloway, Marius C. Hoener, Mark D. Berry, Craig S. Moore
Summary: The expression of TAAR1 is found to be decreased in MS patients, while its localization and function are altered under different conditions. This suggests a potential important role of TAAR1 in the pathophysiology of MS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Karolina E. Kolaczynska, Dino Luethi, Daniel Trachsel, Marius C. Hoener, Matthias E. Liechti
Summary: The psychedelic alkaloids, scalines and 3C-scalines, were found to have similar effects to mescaline and could potentially be used as novel therapeutics for psychedelic-assisted therapy. These compounds interacted with various monoamine receptors, with higher affinity observed at 5-HT2A and 5-HT2C receptors.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Karolina E. Kolaczynska, Paula Ducret, Daniel Trachsel, Marius C. Hoener, Matthias E. Liechti, Dino Luethi
Summary: This article examines the pharmacological properties of MDA analogs and related amphetamine-based compounds, including monoamine uptake inhibition and release, as well as transporter and receptor binding and activation properties. The study finds that some MDA analogs have similar pharmacological profiles to MDMA, while others have more pronounced dopaminergic activity. Further research on the pharmacokinetics and pharmacodynamics of these drugs is needed to better evaluate their risks and therapeutic potential.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Dino Luethi, Deborah Rudin, Marius C. Hoener, Mattias E. Liechti
Meeting Abstract
Biochemistry & Molecular Biology
Deborah Rudin, Dino Luethi, Marius C. Hoener, Matthias E. Liechti
Article
Biochemistry & Molecular Biology
Daniil Grinchii, Marius C. Hoener, Talah Khoury, Roman Dekhtiarenko, Reyhaneh Nejati Bervanlou, Daniela Jezova, Eliyahu Dremencov
Summary: Trace amine-associated receptor 1 (TAAR1) has been identified as a potential target for future antidepressant, antipsychotic, and anti-addiction drugs. Studies have shown that TAAR1 agonists can produce antidepressant, antipsychotic, and anti-addiction behavioral effects in rodents and primates, and these effects are associated with the modulation of serotonin (5-HT) and dopamine.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
David A. Barnes, Marius C. Hoener, Craig S. Moore, Mark D. Berry
Summary: This study reveals the role of Trace amine-associated receptor 1 (TAAR1) in modulating cytokine secretion and metabolic profiles in peripherally-derived macrophages. It also suggests a potential therapeutic target for inflammatory disorders. However, TAAR1 does not have the same effect in CNS-resident macrophages.
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2023)
Article
Neurosciences
Adam L. Halberstadt, Dino Luethi, Marius C. Hoener, Daniel Trachsel, Simon D. Brandt, Matthias E. Liechti
Summary: This study investigated the structure-activity relationships of 4-thio-substituted phenylalkylamines and found that these compounds have psychedelic effects, supporting their classification as psychedelics.
PSYCHOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bartosz Adam Frycz, Klaudia Nowicka, Anna Konopka, Marius Christian Hoener, Ewa Bulska, Leszek Kaczmarek, Marzena Stefaniuk
Summary: Alcohol dependence is characterized by abnormal dopamine release in the brain. TAAR1, a receptor that regulates dopamine neurotransmission, may be a target for treating addiction. This study examined the effects of TAAR1 activation on alcohol consumption in mice and found that activation of TAAR1 reduces alcohol drinking and preference. The findings suggest that TAAR1 is a promising target for treating alcohol abuse and relapse.
Review
Neurosciences
Ahmed Haider, Nehal H. Elghazawy, Alyaa Dawood, Catherine Gebhard, Thomas Wichmann, Wolfgang Sippl, Marius Hoener, Ernest Arenas, Steven H. Liang
Summary: Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily affecting the elderly. PD is characterized by nigrostriatal loss and the formation of misfolded alpha-synuclein protein aggregates. Motor symptoms can be managed with dopaminergic therapy initially, but ultimately become unresponsive. Molecular imaging techniques such as PET and SPECT can be used to study PD.
MOLECULAR NEURODEGENERATION
(2023)
Correction
Neurosciences
Anushka V. Goonawardena, Stephen R. Morairty, Ryan Dell, Gabriel A. Orellana, Marius C. Hoener, Tanya L. Wallace, Thomas S. Kilduff
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Cell Biology
Nikhil J. Pandya, Congwei Wang, Veronica Costa, Paul Lopatta, Sonja Meier, F. Isabella Zampeta, A. Mattijs Punt, Edwin Mientjes, Philip Grossen, Tania Distler, Manuel Tzouros, Yasmina Marti, Balazs Banfai, Christoph Patsch, Soren Rasmussen, Marius Hoener, Marco Berrera, Thomas Kremer, Tom Dunkley, Martin Ebeling, Ben Distel, Ype Elgersma, Ravi Jagasia
Summary: Angelman syndrome is a neurodevelopmental disorder caused by the loss of maternal UBE3A, and studying neurons derived from patients with AS and neurotypical individuals have revealed the potential involvement of the protein PEG10 in AS pathophysiology. Further research on PEG10 and its interaction with RNA and certain proteins may shed light on the mechanisms underlying this disorder.
CELL REPORTS MEDICINE
(2021)
Meeting Abstract
Pharmacology & Pharmacy
David Barnes, Marius Hoener, Craig Moore, Mark Berry
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Clinical Neurology
Hannah Meijs, Helena Voetterl, Alexander T. Sack, Hanneke van Dijk, Bieke De Wilde, Jan Van Hecke, Peter Niemegeers, Evian Gordon, Jurjen J. Luykx, Martijn Arns
Summary: This study used a polygenic score (PGS) and electroencephalography (EEG) data analysis to identify potential predictors for treatment outcomes in major depressive disorder (MDD). The results suggest the existence of a stable EEG network related to antidepressant-response that has potential as a predictor for MDD treatment, particularly in the case of venlafaxine.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2024)