4,691 results match your criteria Toxicity Neuroleptic Agents


CB1R-stabilized NLRP3 inflammasome drives antipsychotics cardiotoxicity.

Signal Transduct Target Ther 2022 Jun 24;7(1):190. Epub 2022 Jun 24.

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.

Long-term use of antipsychotics is a common cause of myocardial injury and even sudden cardiac deaths that often lead to drug withdrawn or discontinuation. Mechanisms underlying antipsychotics cardiotoxicity remain largely unknown. Herein we performed RNA sequencing and found that NLRP3 inflammasome-mediated pyroptosis contributed predominantly to multiple antipsychotics cardiotoxicity. Read More

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Metabolic profiling of lysophosphatidylcholines in chlorpromazine hydrochloride- and -acetyl--amino-phenoltriptolide-induced liver injured rats based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

Hum Exp Toxicol 2022 Jan-Dec;41:9603271221108320

School of Pharmacy, 177505Jiangxi Science and Technology Normal University, Nanchang, P.R. China.

Chlorpromazine hydrochloride (CH) and -acetyl--amino-phenoltriptolide (APAP) are typical acentral dopamine receptor antagonists and antipyretic analgesics in clinical applications, respectively. However, it has been reported that these 2 drugs could cause liver damage. Lysophosphatidylcholines (LPCs) have multiple physiological functions and are metabolized primarily in the liver, where it undergoes significant changes when the liver is damaged. Read More

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The overall assessment of simultaneous photocatalytic degradation of Cimetidine and Amisulpride by using chemical and genotoxicological approaches.

Sci Total Environ 2022 Sep 21;838(Pt 3):156140. Epub 2022 May 21.

Department of Environmental Engineering, University of Patras, GR-30100 Agrinio, Greece. Electronic address:

Pharmaceutical Active Compounds (PhACs) are of particular interest among the emerging contaminants detected in the aquatic environment. Commonly, PhACs exist as complex mixtures in aquatic systems, causing potential adverse effects to the environment and human health than those of individual compounds. Based on the increasing interest in the contamination of water resources by PhACs, the photocatalytic degradation of Cimetidine and Amisulpride as a mixture in combination with their toxic and genotoxic effects before and after the treatment were evaluated for the first time. Read More

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September 2022

Pegylation of phenothiazine - A synthetic route towards potent anticancer drugs.

J Adv Res 2022 03 9;37:279-290. Epub 2021 Jul 9.

Petru Poni" Institute of Macromolecular Chemistry of Romanian Academy, Iasi, Romania.

Introduction: Cancer is a big challenge of the 21 century, whose defeat requires efficient antitumor drugs.

Objectives: The paper aims to investigate the synergistic effect of two structural building blocks, phenothiazine and poly(ethylene glycol), towards efficient antitumor drugs.

Methods: Two PEGylated phenothiazine derivatives were synthetized by attaching poly(ethylene glycol) of 550 Da to the nitrogen atom of phenothiazine by ether or ester linkage. Read More

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The Impact of the Antipsychotic Medication Chlorpromazine on Cytotoxicity through Ca Signaling Pathway in Glial Cell Models.

Neurotox Res 2022 Jun 19;40(3):791-802. Epub 2022 Apr 19.

Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 81362, Taiwan.

Chlorpromazine, an antipsychotic medication, is conventionally applied to cope with the psychotic disorder such as schizophrenia. In cellular studies, chlorpromazine exerts many different actions through calcium ion (Ca) signaling, but the underlying pathways are elusive. This study explored the effect of chlorpromazine on viability, Ca signaling pathway and their relationship in glial cell models (GBM 8401 human glioblastoma cell line and Gibco® Human Astrocyte (GHA)). Read More

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Combined Levo-tetrahydropalmatine and diphenyleneiodonium chloride enhances antitumor activity in hepatocellular carcinoma.

Pharmacol Res 2022 05 10;179:106219. Epub 2022 Apr 10.

Department of Chemistry and Physics, Stony Brook University, Stony Brook, NY 11794-3400, USA. Electronic address:

Metabolic dysregulation is a hallmark of hepatocellular carcinoma (HCC). AMPK is a crucial hub of metabolic regulation during cancer progression. We show that phytochemical Levo-tetrahydropalmatine (THP) activates AMPK-dependent autophagy to downregulate the mitochondrial respiration and glycolysis. Read More

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In vitro and in vivo evaluation of antioxidant and neuroprotective properties of antipsychotic D2AAK1.

Neurochem Res 2022 Jun 5;47(6):1778-1789. Epub 2022 Apr 5.

Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Laboratory, Faculty of Pharmacy, Medical University of Lublin, 4A Chodzki St, 20-093, Lublin, Poland.

The susceptibility of neurons to free radical toxicity partially underlies the pathomechanism of neurodegenerative diseases. On the other hand, excitotoxicity also contributes to neurodegeneration. Our previous studies demonstrated the unique properties of D2AAK1 as a potent multi-target ligand of aminergic G protein-coupled receptors (GPCRs) which dose-dependently stimulates growth, survival of neurons, and promotes their integrity. Read More

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Striatal Neuronal Ensembles Reveal Differential Actions of Amantadine and Clozapine to Ameliorate Mice L-DOPA-Induced Dyskinesia.

Neuroscience 2022 06 30;492:92-107. Epub 2022 Mar 30.

División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City 04510, Mexico. Electronic address:

Amantadine and clozapine have proved to reduce abnormal involuntary movements (AIMs) in preclinical and clinical studies of L-DOPA-Induced Dyskinesias (LID). Even though both drugs decrease AIMs, they may have different action mechanisms by using different receptors and signaling profiles. Here we asked whether there are differences in how they modulate neuronal activity of multiple striatal neurons within the striatal microcircuit at histological level during the dose-peak of L-DOPA in ex-vivo brain slices obtained from dyskinetic mice. Read More

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Human Retinal Organoids Provide a Suitable Tool for Toxicological Investigations: A Comprehensive Validation Using Drugs and Compounds Affecting the Retina.

Stem Cells Transl Med 2022 03;11(2):159-177

Newcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.

Retinal drug toxicity screening is essential for the development of safe treatment strategies for a large number of diseases. To this end, retinal organoids derived from human pluripotent stem cells (hPSCs) provide a suitable screening platform due to their similarity to the human retina and the ease of generation in large-scale formats. In this study, two hPSC cell lines were differentiated to retinal organoids, which comprised all key retinal cell types in multiple nuclear and synaptic layers. Read More

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Improving the treatment of Parkinson's disease: Structure-based development of novel 5-HT receptor antagonists/inverse agonists.

Eur J Med Chem 2022 Apr 2;234:114246. Epub 2022 Mar 2.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China. Electronic address:

Pimavanserin is a selective 5-HT receptor antagonist and inverse agonist approved by the FDA in 2016, which is used to treat patients with Parkinson's disease psychosis (PDP). But pimavanserin has potential risk with increasing mortality in elderly patients and also increasing the risk of QT interval prolongation in patients. Therefore, searching for new drugs with high efficacy and low toxicity is urgently needed. Read More

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Label-free quantitative proteomic analysis of reserpine-induced depression in mice intervened by berberine.

Pak J Pharm Sci 2022 Jan;35(1):151-155

Jiangsu Plant Medicine Research and Development Center, Nanjing University of Chinese Medicine, Nanjing, China.

Proteomic analysis of reserpine-induced depression and the effects of berberine on this were investigated to delineate the possible underlying mechanism. Reserpine was used for the model of behavioral depression. Model mice were treated with berberine. Read More

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January 2022

Exposure to anti-seizure medications impact growth of gut bacterial species and subsequent host response.

Neurobiol Dis 2022 06 17;167:105664. Epub 2022 Feb 17.

Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Domaine de Vilvert, Jouy-en-Josas 78350, France. Electronic address:

Anti-seizure medications (ASMs) are the first line of treatment for seizure control in children with epilepsy. Cumulative evidence suggests an imbalanced gut microbiota in refractory epilepsy patients. We systematically investigated the differential antimicrobial impacts of nine ASM active ingredients, seven common excipients of ASMs, and four syrup formulations on core early-life gut microbiota strains. Read More

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Recognition and management of clozapine adverse effects: A systematic review and qualitative synthesis.

Acta Psychiatr Scand 2022 05 16;145(5):423-441. Epub 2022 Mar 16.

VA Boston Healthcare System, Boston, Massachusetts, USA.

Objective: Clozapine is substantially underutilized in most countries and clinician factors including lack of knowledge and concerns about adverse drug effects (ADEs) contribute strongly to treatment reluctance. The aim of this systematic review was to provide clinicians with a comprehensive information source regarding clozapine ADEs.

Methods: PubMed and Embase databases were searched for English language reviews concerned with clozapine ADEs; publications identified by the automated search were manually searched for additional relevant citations. Read More

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Novel D/5-HT receptor modulators related to cariprazine with potential implication to schizophrenia treatment.

Eur J Med Chem 2022 Mar 9;232:114193. Epub 2022 Feb 9.

National Institute of Mental Health, Topolova 748, Klecany, 250 67, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic. Electronic address:

Schizophrenia is a serious mental disorder without a fully understood pathomechanism, but which involves dysregulation of neurotransmitters and their receptors. The best option for the management of schizophrenia comprises so-called multi-target ligands, similar to the third generation of neuroleptics. Dopamine type 2 receptors (DRs) are the main target in the treatment of schizophrenia, in particular for mitigation of the positive symptoms. Read More

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Haloperidol alters the behavioral, hematological and biochemical parameters of freshwater African catfish, Clarias gariepinus (Burchell 1822).

Comp Biochem Physiol C Toxicol Pharmacol 2022 Apr 31;254:109292. Epub 2022 Jan 31.

Department of Zoology and Environmental Biology, University of Nigeria Nsukka, Enugu, Nigeria. Electronic address:

The presence of drugs and their metabolites in surface waters and municipal effluents has been reported in several studies, but their impacts on aquatic organisms are not yet well studied. The present study investigated the effects of exposure to the antipsychotic drug, haloperidol on the behavioral, hematological and biochemical parameters in juvenile Clarias gariepinus. The fishes were exposed to 0. Read More

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Effects of a Novel UGT2B Haplotype and UGT1A4*3 Allele Variants on Glucuronidation of Clozapine In vivo.

Curr Drug Metab 2022 ;23(1):66-72

Center for Psychopharmacology, Diakonhjemmet Hospital, PO Box 85, Vinderen, 0319 Oslo, Norway.

Background: Glucuronidation is an important metabolic pathway of clozapine (CLZ), but the impact of various uridine 5'diphospho-glucuronosyltransferases (UGT) polymorphisms on the exposure and metabolism of CLZ in vivo is unclear.

Objective: The objective of this study was to investigate the impact of UGT2B haplotype and UGT1A4*3 allele variants on the formation of CLZ glucuronide metabolites (5N- and N+-glucuronide) and CLZ exposure in patients' serum after adjusting for sex, age, and smoking habits.

Methods: The study was based on serum samples from CLZ-treated patients (n=79) subjected to routine therapeutic drug monitoring (TDM) at Diakonhjemmet Hospital, Oslo, Norway. Read More

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Effects of Low- and High-Dose Valproic Acid and Lamotrigine on the Heart in Female Rats.

Cardiovasc Toxicol 2022 04 22;22(4):326-340. Epub 2022 Jan 22.

Department of Histology and Embriyology, Faculty of Medicine, Firat University, Elazig, Turkey.

Epilepsy is a chronic neurological disease that affects more than 50 million people worldwide. Antiepileptic drugs (AEDs) are the mainstay of treatment for most patients with epilepsy. However, AEDs have been reported to be associated with adverse cardiac effects. Read More

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Association between myocarditis and antipsychotics other than clozapine: a systematic literature review and a pharmacovigilance study using VigiBase.

Expert Rev Clin Pharmacol 2022 Jan 27;15(1):65-78. Epub 2022 Jan 27.

Mental Health Research Center at Eastern State Hospital, Lexington, KY, USA.

Introduction: Pharmacovigilance studies have definitely established that clozapine can cause myocarditis. Two published reviews suggested that on rare occasions other antipsychotics may induce myocarditis.

Areas Covered: This review explored myocarditis associated with antipsychotics other than clozapine by conducting a systematic search of the literature and critically analyzing the current data in VigiBase compared to the data on clozapine-associated myocarditis. Read More

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January 2022

Clozapine toxicity and coronavirus disease 2019: A case report.

Schizophr Res 2022 02 10;240:184-185. Epub 2022 Jan 10.

Department of Psychiatry and Psychology, Institute of Neuroscience, Hospital Clínic of Barcelona, Catalonia, C/ Villarroel - 170, 08036 Barcelona, Spain. Electronic address:

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February 2022

Activation of the aryl hydrocarbon receptor by clozapine induces preadipocyte differentiation and contributes to endothelial dysfunction.

J Psychopharmacol 2022 02 3;36(2):191-201. Epub 2022 Jan 3.

Neurobiochemical Research Unit, Department of Psychiatry, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Background: The superior therapeutic benefit of clozapine is often associated with metabolic disruptions as obesity, insulin resistance, tachycardia, higher blood pressure, and even hypertension.

Aims: These adverse vascular/ metabolic events under clozapine are similar to those caused by polycyclic aromatic hydrocarbons (PAHs), and clozapine shows structural similarity to well-known ligands of the aryl hydrocarbon receptor (AhR). Therefore, we speculated that the side effects caused by clozapine might rely on AhR signaling. Read More

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February 2022

Clozapine modulation of zebrafish swimming behavior and gene expression as a case study to investigate effects of atypical drugs on aquatic organisms.

Sci Total Environ 2022 Apr 27;815:152621. Epub 2021 Dec 27.

Department of Ecosystem Analysis, Institute for Environmental Research, ABBt-Aachen Biology and Biotechnology, RWTH Aachen University, 52074 Aachen, Germany; Department Evolutionary Ecology and Environmental Toxicology, Faculty Biological Sciences, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany. Electronic address:

Mental illnesses affect more than 150 million people in Europe and lead to an increasing consumption of neuroactive drugs during the last twenty years. The antipsychotic compound, clozapine, is one of the most used psychotropic drugs worldwide, with potentially negative consequences for the aquatic environment. Hence, the objectives of the study presented here were the quantification of clozapine induced changes in swimming behavior of exposed Danio rerio embryos and the elucidation of the molecular effects on the serotonergic and dopaminergic systems. Read More

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Antiepileptic drugs lamotrigine and valproate differentially affect neuronal maturation in the developing chick embryo, yet with PAX6 as a potential common mediator.

Neurotoxicol Teratol 2022 Mar-Apr;90:107057. Epub 2021 Dec 20.

Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway. Electronic address:

Exposing the immature nervous system to specific antiepileptic drugs (AEDs) during pregnancy is linked to neurodevelopmental disorders such as autism spectrum disorder (ASD). Newer AEDs like lamotrigine (LTG) are hailed as safer, but recent epidemiological data suggest that even LTG carries a risk, although much lower than that associated with valproic acid (VPA), an older AED, which is also known to cause morphological alterations in the developing brain. Increasing evidence highlights cerebellar abnormalities as important in ASD pathophysiology. Read More

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Clozapine Induces an Acute Proinflammatory Response That Is Attenuated by Inhibition of Inflammasome Signaling: Implications for Idiosyncratic Drug-Induced Agranulocytosis.

Toxicol Sci 2022 02;186(1):70-82

Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada.

Although clozapine is a highly efficacious schizophrenia treatment, it is under-prescribed due to the risk of idiosyncratic drug-induced agranulocytosis (IDIAG). Clinical data indicate that most patients starting clozapine experience a transient immune response early in treatment and a similar response has been observed in clozapine-treated rats, but the mechanism by which clozapine triggers this transient inflammation remains unclear. Therefore, the aim of this study was to characterize the role of inflammasome activation during the early immune response to clozapine using in vitro and in vivo models. Read More

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February 2022

An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.

Pharmacopsychiatry 2022 Mar 15;55(2):73-86. Epub 2021 Dec 15.

Department of Physical Medicine and Pharmacology, School of Medicine, Universidad de La Laguna, Canary Islands, Spain.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Read More

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[Anticholinergic scales: Use in psychiatry and update of the anticholinergic impregnation scale].

Encephale 2022 Jun 4;48(3):313-324. Epub 2021 Dec 4.

Pôle hospitalo-universitaire de psychiatrie d'adultes du Grand Nancy, Centre psychothérapique de Nancy, 54520 Laxou, France; Département de neurologie, CHU de Nancy, 54000 Nancy, France.

Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Read More

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Chemogenetic Seizure Control with Clozapine and the Novel Ligand JHU37160 Outperforms the Effects of Levetiracetam in the Intrahippocampal Kainic Acid Mouse Model.

Neurotherapeutics 2022 01 3;19(1):342-351. Epub 2021 Dec 3.

4BRAIN, Department of Neurology, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium.

Expression of inhibitory designer receptors exclusively activated by designer drugs (DREADDs) on excitatory hippocampal neurons in the hippocampus represents a potential new therapeutic strategy for drug-resistant epilepsy. To overcome the limitations of the commonly used DREADD agonist clozapine, we investigated the efficacy of the novel DREADD ligand JHU37160 in chemogenetic seizure suppression in the intrahippocampal kainic acid (IHKA) mouse model for temporal lobe epilepsy (TLE). In addition, seizure-suppressing effects of chemogenetics were compared to the commonly used anti-epileptic drug (AED), levetiracetam (LEV). Read More

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January 2022

Lamotrigine effects on immune gene expression in larval zebrafish.

Epilepsy Res 2021 12 23;178:106823. Epub 2021 Nov 23.

Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. Box 5003, 1432 Ås, Norway.

Purpose: Despite growing evidence that neuroinflammation and pro-inflammatory cytokines are involved in the pathogenesis of seizures and epilepsy, this knowledge has not been incorporated in the proposed mechanism of action of any of the current antiseizure medications (ASMs). Here, we tested the hypothesis by assessing inflammation markers in larval zebrafish (Danio rerio) exposed to lamotrigine (LTG).

Methods: In order to establish the most appropriate LTG concentrations for the transcriptome analysis (RNAseq), we initially assessed for teratogenic (spinal cord deformation, heart oedema, failed inflation of the swim bladder) and behavioural effects (distance moved, time spent active, and average swimming speed during a light/dark test) in zebrafish larvae exposed to 0, 50, 100, 300, 500, 750, and 1000 μM LTG continuously between 5 and 120 h post fertilisation. Read More

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December 2021

Toxic effect of antidepressants on male reproductive system cells: evaluation of possible fertility reduction mechanism.

J Physiol Pharmacol 2021 Jun 19;72(3). Epub 2021 Nov 19.

Department of Biotechnology, Institute of Biology and Biotechnology, University of Rzeszow, Rzeszow, Poland.

Depression is acknowledged as a major public health problem. Pharmacological treatment may cause adverse drug reactions and sexual side effects. At the same time, the knowledge of the molecular mechanisms associated with antidepressant-mediated toxicity to reproductive cells is fragmentary. Read More

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