International Journal of Molecular Sciences

Impact of Two Neuronal Sigma-1 Receptor Modulators, PRE084 and DMT, on Neurogenesis and Neuroinflammation in an Aβ1–42-Injected, Wild-Type Mouse Model of AD

International Journal of Molecular Sciences February 24, 2022 Emőke Borbély, Viktória É Varga, Titanilla Szögi et al. 31 citations

Alzheimer’s disease (AD) is the most common form of dementia characterized by cognitive dysfunctions. Pharmacological interventions to slow the progression of AD are intensively studied. A potential direction targets neuronal sigma-1 receptors (S1Rs). S1R ligands are recognized as promising therapeutic agents that may alleviate symptom severity of AD, possibly via preventing amyloid-β-(Aβ-)...

DOI: 10.3390/ijms23052514 Neurogenesis Sigma-1 receptor Neuroinflammation Astrogliosis +2

Intriguing Cytotoxicity of the Street Dissociative Anesthetic Methoxphenidine: Unexpected Impurities Spotted

International Journal of Molecular Sciences February 14, 2022 Bronislav Jurásek, Silvie Rimpelová, Martin Babor et al. 7 citations

The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate...

DOI: 10.3390/ijms23042083 Cytotoxicity Impurity Dissociative Powder diffraction +6

Overcoming Depression with 5-HT2A Receptor Ligands

International Journal of Molecular Sciences December 21, 2021 Agata Zięba, Piotr Stępnicki, Dariusz Matosiuk et al. 55 citations

Depression is a multifactorial disorder that affects millions of people worldwide, and none of the currently available therapeutics can completely cure it. Thus, there is a need for developing novel, potent, and safer agents. Recent medicinal chemistry findings on the structure and function of the serotonin 2A (5-HT2A) receptor facilitated design and discovery of novel compounds with...

DOI: 10.3390/ijms23010010 Virtual screening Receptor Depression economics Antidepressant +3

Interaction Profiles of Central Nervous System Active Drugs at Human Organic Cation Transporters 1-3 and Human Plasma Membrane Monoamine Transporter.

International Journal of Molecular Sciences November 30, 2021 Thomas J F Angenoorth, Stevan Stankovic, Marco Niello et al. 18 citations

Many psychoactive compounds have been shown to primarily interact with high-affinity and low-capacity solute carrier 6 (SLC6) monoamine transporters for norepinephrine (NET; norepinephrine transporter), dopamine (DAT; dopamine transporter) and serotonin (SERT; serotonin transporter). Previous studies indicate an overlap between the inhibitory capacities of substances at SLC6 and SLC22 human...

DOI: 10.3390/ijms222312995 Full text Ketamine Psilocybin O-desmethyltramadol Bupropion +5

Many Drugs of Abuse May Be Acutely Transformed to Dopamine, Norepinephrine and Epinephrine In Vivo

International Journal of Molecular Sciences October 2, 2021 Paul J. Fitzgerald 30 citations

It is well established that a wide range of drugs of abuse acutely boost the signaling of the sympathetic nervous system and the hypothalamic–pituitary–adrenal (HPA) axis, where norepinephrine and epinephrine are major output molecules. This stimulatory effect is accompanied by such symptoms as elevated heart rate and blood pressure, more rapid breathing, increased body temperature and...

DOI: 10.3390/ijms221910706 Dopamine Norepinephrine In vivo Pharmacology +2

Low Doses of Ketamine and Melatonin in Combination Produce Additive Antidepressant-like Effects in Mice

International Journal of Molecular Sciences August 26, 2021 Rosa Estrada-Reyes, Daniel Quero-Chávez, Citlali Trueta et al.

Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously,...

DOI: 10.3390/ijms22179225 Full text

Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats

International Journal of Molecular Sciences August 18, 2021 Marina Gabaglio, Erica Zamberletti, Cristina Manenti et al.

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids...

DOI: 10.3390/ijms22168899

The Pharmacological Profile of Second Generation Pyrovalerone Cathinones and Related Cathinone Derivative

International Journal of Molecular Sciences July 31, 2021 Karolina E. Kolaczynska, Jan Thomann, Marius C. Hoener et al. 35 citations

Pyrovalerone cathinones are potent psychoactive substances that possess a pyrrolidine moiety. Pyrovalerone-type novel psychoactive substances (NPS) are continuously detected but their pharmacology and toxicology are largely unknown. We assessed several pyrovalerone and related cathinone derivatives at the human norepinephrine (NET), dopamine (DAT), and serotonin (SERT) uptake transporters using...

DOI: 10.3390/ijms22158277 Cathinone Pharmacology Potency Dopamine transporter +4

In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP.

International Journal of Molecular Sciences July 17, 2021 Sabrine Bilel, Micaela Tirri, Raffaella Arfè et al.

1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and...

DOI: 10.3390/ijms22147659 Full text 1-cyclohexyl-x-methoxybenzene Pcp Behavior Mice +3

Biomolecular Basis of Cellular Consciousness via Subcellular Nanobrains

International Journal of Molecular Sciences March 3, 2021 František Baluška, William B. Miller, Arthur S. Reber 96 citations

Cells emerged at the very beginning of life on Earth and, in fact, are coterminous with life. They are enclosed within an excitable plasma membrane, which defines the outside and inside domains via their specific biophysical properties. Unicellular organisms, such as diverse protists and algae, still live a cellular life. However, fungi, plants, and animals evolved a multicellular existence....

DOI: 10.3390/ijms22052545 Multicellular organism Sentience Consciousness Algae +5

Chemistry and Toxicology of Major Bioactive Substances in Inocybe Mushrooms

International Journal of Molecular Sciences February 23, 2021 Jiří Patočka, Ran Wu, Eugenie Nepovimová et al. 45 citations

Mushroom poisoning has always been a threat to human health. There are a large number of reports about ingestion of poisonous mushrooms every year around the world. It attracts the attention of researchers, especially in the aspects of toxin composition, toxic mechanism and toxin application in poisonous mushroom. Inocybe is a large genus of mushrooms and contains toxic substances including...

DOI: 10.3390/ijms22042218 Psilocybin Mushroom Agaricales Muscarine +1

A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain

International Journal of Molecular Sciences January 15, 2021 Nakul Ravi Raval, Annette Johansen, Lene Lundgaard Donovan et al. 191 citations

A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could be linked to increased synaptogenesis and down-regulation of cerebral 5-HT2AR. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and...

DOI: 10.3390/ijms22020835 Psilocybin Hallucinogen Pharmacology

Novel Psychoactive Phenethylamines: Impact on Genetic Material.

International Journal of Molecular Sciences December 17, 2020 Veronica Cocchi, Sofia Gasperini, Patrizia Hrelia et al. 32 citations

Psychedelic and stimulating phenethylamines belong to the family of new psychoactive substances (NPS). The acute toxicity framework has begun to be investigated, while studies showing genotoxic potential are very limited or not available. Therefore, in order to fill this gap, the aim of the present work was to evaluate the genotoxicity by treating TK6 cells with 2C-H, 2C-I, 2C-B, 25B-NBOMe, and...

DOI: 10.3390/ijms21249616 Full text MDMA 25b-nbome 2c-b 2c-h +9

Toxicology and Analysis of Psychoactive Tryptamines

International Journal of Molecular Sciences December 4, 2020 Sara Malaca, Alfredo Fabrizio Lo Faro, Alice Tamborra et al. 48 citations

Our understanding of tryptamines is poor due to the lack of data globally. Tryptamines currently are not part of typical toxicology testing regimens and their contribution to drug overdoses may be underestimated. Although their prevalence was low, it is increasing. There are few published data on the many new compounds, their mechanisms of action, onset and duration of action, toxicity, signs...

DOI: 10.3390/ijms21239279 Tryptamines Pharmacology Toxicology

Candidate Strategies for Development of a Rapid-Acting Antidepressant Class That Does Not Result in Neuropsychiatric Adverse Effects: Prevention of Ketamine-Induced Neuropsychiatric Adverse Reactions

International Journal of Molecular Sciences October 26, 2020 Motohiro Okada, Yasuhiro Kawano, Kouji Fukuyama et al. 31 citations

Non-competitive N-methyl-D-aspartate/glutamate receptor (NMDAR) antagonism has been considered to play important roles in the pathophysiology of schizophrenia. In spite of severe neuropsychiatric adverse effects, esketamine (racemic enantiomer of ketamine) has been approved for the treatment of conventional monoaminergic antidepressant-resistant depression. Furthermore, ketamine improves...

DOI: 10.3390/ijms21217951 Ketamine Serotonin Anxiety Monoaminergic +8

Serotonin Transporter and Plasma Membrane Monoamine Transporter Are Necessary for the Antidepressant-Like Effects of Ketamine in Mice

International Journal of Molecular Sciences October 1, 2020 M. Bowman, M. Vitela, K. Clarke et al.

Major depressive disorder is typically treated with selective serotonin reuptake inhibitors (SSRIs), however, SSRIs take approximately six weeks to produce therapeutic effects, if any. Not surprisingly, there has been great interest in findings that low doses of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produce rapid and long-lasting antidepressant effects....

DOI: 10.3390/ijms21207581 Full text

Total Recall: Lateral Habenula and Psychedelics in the Study of Depression and Comorbid Brain Disorders

International Journal of Molecular Sciences September 7, 2020 Matas Vitkauskas, Ajay S. Mathuru 4 citations

Depression impacts the lives and daily activities of millions globally. Research into the neurobiology of lateral habenula circuitry and the use of psychedelics for treating depressive states has emerged in the last decade as new directions to devise interventional strategies and therapies. Several clinical trials using deep brain stimulation of the habenula, or using ketamine, and psychedelics...

DOI: 10.3390/ijms21186525 Psilocybin Serotonergic Habenula Neuroimaging +6

The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4'-F-PCP) in Rodents.

International Journal of Molecular Sciences June 29, 2020 In Soo Ryu, Oc-Hee Kim, Young Eun Lee et al.

The dissociative anesthetic phencyclidine (PCP) and PCP derivatives, including 4'-F-PCP, are illegally sold and abused worldwide for recreational and non-medical uses. The psychopharmacological properties and abuse potential of 4'-F-PCP have not been fully characterized. In this study, we evaluated the psychomotor, rewarding, and reinforcing properties of 4'-F-PCP using the open-field test,...

DOI: 10.3390/ijms21134631 Full text Abuse potential Conditioned place preference Designer drugs Phencyclidine pcp derivatives +1

Para-Halogenation of Amphetamine and Methcathinone Increases the Mitochondrial Toxicity in Undifferentiated and Differentiated SH-SY5Y Cells

International Journal of Molecular Sciences April 18, 2020 Xun Zhou, Jamal Bouitbir, Matthias E. Liechti et al. 29 citations

Halogenation of amphetamines and methcathinones has become a common method to obtain novel psychoactive substances (NPS) also called “legal highs”. The para-halogenated derivatives of amphetamine and methcathinone are available over the internet and have entered the illicit drug market but studies on their potential neurotoxic effects are rare. The primary aim of this study was to explore the...

DOI: 10.3390/ijms21082841 Sh-sy5y Amphetamine Pharmacology Neurotoxicity +11

Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration

International Journal of Molecular Sciences March 20, 2020 David P. Herzog, Ratnadevi M. Mellema, Floortje Remmers et al. 9 citations

Background: Rapid-acting antidepressants ketamine and (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) have overcome some of the major limitations of classical antidepressants. However, little is known about sex-specific differences in the behavioral and molecular effects of ketamine and (2R,6R)-HNK in rodents. Methods: We treated mice with an intraperitoneal injection of either saline, ketamine (30 mg...

DOI: 10.3390/ijms21062142 Ketamine Anxiety Arc geometry Behavioural despair test +11

Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats

International Journal of Molecular Sciences March 12, 2019 Stefania Schiavone, Margherita Neri, Angela Bruna Maffione et al. 22 citations

Several mechanisms underlying 3,4-Methylenedioxy-N-methylamphetamine (MDMA) neurotoxicity have been proposed, including neurochemical alterations and excitotoxicity mediated by reactive oxygen species (ROS), nitric oxide (NO), and reactive nitrogen species (RNS). However, ROS, NO, and RNS sources in the brain are not fully known. We aimed to investigate possible alterations in the expression of...

DOI: 10.3390/ijms20051242 MDMA Dopaminergic Pharmacology Oxidative stress

Morphing of Ibogaine: A Successful Attempt into the Search for Sigma-2 Receptor Ligands.

International Journal of Molecular Sciences January 23, 2019 Giuseppe Floresta, Maria Dichiara, Davide Gentile et al. 16 citations

Ibogaine is a psychoactive indole alkaloid with high affinity for several targets including the σ₂ receptor. Indeed, extensive data support the involvement of the σ₂ receptor in neurological disorders, including Alzheimer's disease, schizophrenia, alcohol abuse and pain. Due to its serious side effects which prevent ibogaine from potential clinical applications, novel ibogaine derivatives...

DOI: 10.3390/ijms20030488 Full text Ibogaine Incazane Pinoline Tmem97 +5

Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors

International Journal of Molecular Sciences September 23, 2018 Domenico de Berardis, Michele Fornaro, Alessandro Valchera et al. 171 citations

Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is...

DOI: 10.3390/ijms19102888 Ketamine Anxiety Suicidal ideation Mood disorders +5

Ketamine Analog Methoxetamine Induced Inflammation and Dysfunction of Bladder in Rats

International Journal of Molecular Sciences January 18, 2017 Qiang Wang, Qinghui Wu, Junpeng Wang et al.

The novel synthetic psychoactive ketamine analog methoxetamine is reportedly being used for recreational purposes. As ketamine use can result in urinary dysfunction, we conducted the present study to investigate how methoxetamine affects the bladder. A cystometry investigation showed that female Sprague-Dawley rats experienced increased micturition frequency bladder dysfunction after receiving...

DOI: 10.3390/ijms18010117

d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology

International Journal of Molecular Sciences November 23, 2016 Danilo de Gregorio, Stefano Comai, Luca Posa et al. 125 citations

d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles’...

DOI: 10.3390/ijms17111953 Lysergic acid diethylamide Serotonergic Hallucinogen Pharmacology +5

Papers