6,651 results match your criteria Toxicity Sedative-Hypnotics

[Dexmedetomidine-mediated Wnt Pathway Inhibits Sevoflurane-induced Cognitive Impairment in Neonatal Rats].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Apr;43(2):235-246

Department of Anesthesiology,Wuhan No.1 Hospital,Wuhan Hospital of Integrated Traditional Chinese and Western Medicine,Wuhan 430022,China.

Objective To explore the effect of dexmedetomidine(Dex)on sevoflurane-induced cognitive impairment in neonatal rats through Wnt signaling pathway. Methods Sixty 7-day-old SD rats were assigned into five groups:control group(without any intervention),Dex group(intraperitoneal injection of 25 μg/kg Dex),sevoflurane group(3% sevoflurane treatment for 4 hours),sevoflurane+Dex group(inhalation of 3% sevoflurane after injection of 25 μg/kg Dex for 4 hours),and sevoflurane+Dex+Wnt inhibitor group(Wnt inhibitor XAV393 and 25 μg/kg Dex were injected and 3% sevoflurane was inhaled for 4 hours).Three weeks later,Morris water maze was used to detect the cognitive function;TdT-mediated dUTP nick end labeling(TUNEL)staining was performed to detect the apoptosis of hippocampal neurons;neuronal nuclei (NeuN) staining was conducted to detect the survival of hippocampal neurons;Western blot was carried out to detect the expression of apoptosis-related proteins. Read More

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Neuroprotection by delayed triple therapy following sarin nerve agent insult in the rat.

Toxicol Appl Pharmacol 2021 05 3;419:115519. Epub 2021 Apr 3.

Department of Pharmacology, Israel Institute for Biological, Chemical and Environmental Sciences, Ness-Ziona 74100, Israel. Electronic address:

The development of refractory status epilepticus (SE) induced by sarin intoxication presents a therapeutic challenge. In our current research we evaluate the efficacy of a delayed combined triple treatment in ending the abnormal epileptiform seizure activity (ESA) and the ensuing of long-term neuronal insult. SE was induced in male Sprague-Dawley rats by exposure to 1. Read More

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Pharmacology and adverse effects of new psychoactive substances: synthetic cannabinoid receptor agonists.

Arch Pharm Res 2021 Apr 2;44(4):402-413. Epub 2021 Apr 2.

College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaengmyong 1-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk, 28160, Republic of Korea.

Over the last decade, new psychoactive substances (NPS) have continuously been the focus of the international society since their emergence on the illicit drug market. NPS can be classified into six groups including; synthetic cannabinoid receptor agonists (SCRAs), stimulants, opioids, dissociatives, sedatives/hypnotics, and classic hallucinogens with psychoactive effects. These are sold as "herbal incense," "bath salts," "legal highs," and "research chemicals". Read More

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Propofol alleviates inflammation and apoptosis in HCY‑induced HUVECs by inhibiting endoplasmic reticulum stress.

Mol Med Rep 2021 May 24;23(5). Epub 2021 Mar 24.

Department of Anesthesiology, The Affiliated Zhuzhou Hospital of Xiangya School of Medicine CSU, Zhuzhou Central Hospital, Zhuzhou, Hunan 412000, P.R. China.

Atherosclerosis is a chronic vascular inflammatory disease, and is associated with oxidative stress and endothelial dysfunction. Homocysteine (HCY) can cause damage to endothelial cells via the enhancement of the endoplasmic reticulum stress (ERS) pathway. Propofol has a protective effect on endothelial injury and can suppress inflammation and oxidation. Read More

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Effect of dexmedetomidine on sevoflurane-induced neurodegeneration in neonatal rats.

Br J Anaesth 2021 May 12;126(5):1009-1021. Epub 2021 Mar 12.

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Background: Structural brain abnormalities in newborn animals after prolonged exposure to all routinely used general anaesthetics have raised substantial concerns for similar effects occurring in millions of children undergoing surgeries annually. Combining a general anaesthetic with non-injurious sedatives may provide a safer anaesthetic technique. We tested dexmedetomidine as a mitigating therapy in a sevoflurane dose-sparing approach. Read More

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Novel Genetically Modified Mouse Model to Assess Soman-Induced Toxicity and Medical Countermeasure Efficacy: Human Acetylcholinesterase Knock-in Serum Carboxylesterase Knockout Mice.

Int J Mol Sci 2021 Feb 14;22(4). Epub 2021 Feb 14.

Medical Toxicology Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.

The identification of improved medical countermeasures against exposure to chemical warfare nerve agents (CWNAs), a class of organophosphorus compounds, is dependent on the choice of animal model used in preclinical studies. CWNAs bind to acetylcholinesterase and prevent the catalysis of acetylcholine, causing a plethora of peripheral and central physiologic manifestations, including seizure. Rodents are widely used to elucidate the effects of CWNA-induced seizure, albeit with a caveat: they express carboxylesterase activity in plasma. Read More

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February 2021

Behavioral Battery for Testing Candidate Analgesics in Mice. I. Validation with Positive and Negative Controls.

J Pharmacol Exp Ther 2021 05 23;377(2):232-241. Epub 2021 Feb 23.

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA

This study evaluated a battery of pain-stimulated, pain-depressed, and pain-independent behaviors for preclinical pharmacological assessment of candidate analgesics in mice. Intraperitoneal injection of dilute lactic acid (IP acid) served as an acute visceral noxious stimulus to produce four pain-related behaviors in male and female ICR mice: stimulation of 1) stretching, 2) facial grimace, 3) depression of rearing, and 4) depression of nesting. Additionally, nesting and locomotion in the absence of the noxious stimulus were used to assess pain-independent drug effects. Read More

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Reduced hepatic global hydroxymethylation in mice treated with non-genotoxic carcinogens is transiently reversible with a methyl supplemented diet.

Toxicol Appl Pharmacol 2021 03 5;415:115439. Epub 2021 Feb 5.

Investigative Toxicology and Pathology, AbbVie Inc., North Chicago, IL, United States.

Non-genotoxic carcinogens (NGCs) are known to cause perturbations in DNA methylation, which can be an early event leading to changes in gene expression and the onset of carcinogenicity. Phenobarbital (PB) has been shown to alter liver DNA methylation and hydroxymethylation patterns in mice in a time dependent manner. The goals of this study were to assess if clofibrate (CFB), a well-studied rodent NGC, would produce epigenetic changes in mice similar to PB, and if a methyl donor supplementation (MDS) would modulate epigenetic and gene expression changes induced by phenobarbital. Read More

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Depression Part 3: Medication Related Problems.

Sr Care Pharm 2021 02;36(2):68-82

When selecting and managing psychoactive medications in older people, it is equally important to focus on avoidance of toxicity as it is to focus on efficacy. Higher psychoactive medication load is associated with increased rate and risk of all cause hospitalization. The medication classes used to treat depression and related comorbidities include antidepressants, antipsychotics, stimulants, mood stabilizers, lithium, anxiolytics and sedative hypnotics. Read More

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February 2021

Acute lead poisoning: a diagnostic challenge in the emergency department.

BMJ Case Rep 2021 Jan 20;14(1). Epub 2021 Jan 20.

Emergency Medicine, All India Institute of Medical Sciences, New Delhi, Delhi, India

Acute abdominal pain is a common presentation to the emergency department (ED). Ruling out life-threatening causes and giving pain relief are the most important tasks in ED. We describe a 32-year-old man who presented to ED with abdominal pain and vomiting which was unrelieved by usual doses of analgesic. Read More

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January 2021

Photochemical fate of medetomidine in coastal and marine environments.

Water Res 2021 Mar 27;191:116791. Epub 2020 Dec 27.

Department of Environmental Science, Aarhus University, Frederiksborgvej 399, 4000 Roskilde, Denmark; Geological Survey of Denmark and Greenland (GEUS), ØsterVoldgade 10, 1350 Copenhagen, Denmark. Electronic address:

Medetomidine has been authorized in ship hull paints as an antifouling biocide under the biocidal product regulation in Europe since 2016. Its release into marine systems causes concerns over persistence and toxicity. However, the environmental fate of medetomidine has not been fully investigated. Read More

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LMR-101, a novel derivative of propofol, exhibits potent anticonvulsant effects and possibly interacts with a novel target on γ-aminobutyric acid type A receptors.

Epilepsia 2021 01 8;62(1):238-249. Epub 2021 Jan 8.

Department of New Drug Research, Xi'An Libang Pharmaceutical Co, Xi'An, Shaanxi, China.

Objective: LMR-101 is a bisphenol derivative of propofol, a short-acting general anesthetic, which is also used to manage status epilepticus (SE). We evaluated the sedative and anticonvulsant effects of LMR-101 to discover its potential to manage epilepsy and SE in the clinic.

Methods: Comparative studies between LMR-101 and propofol were performed in mice to elucidate an appropriate dose range for LMR-101 that produced anticonvulsant effects without significant sedation. Read More

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January 2021

Propofol ameliorates endotoxin‑induced myocardial cell injury by inhibiting inflammation and apoptosis via the PPARγ/HMGB1/NLRP3 axis.

Mol Med Rep 2021 03 5;23(3). Epub 2021 Jan 5.

Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi 710032, P.R. China.

Endotoxin lipopolysaccharide (LPS) is one of the primary causes of myocardial injury. Propofol confers protective effects against LPS‑induced myocardial damage; however, the biological functions and mechanisms underlying propofol are not completely understood. The present study aimed to investigate the effects of propofol on LPS‑induced myocardial injury. Read More

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Impacts of chronic exposure to sublethal diazepam on behavioral traits of female and male zebrafish (Danio rerio).

Ecotoxicol Environ Saf 2021 Jan 8;208:111747. Epub 2020 Dec 8.

Institute of Environmental Health and Ecological Security, School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Faculty of Agriculture, Kyushu University, Motooka 744, Nishi-ku, Fukuoka 819-0395, Japan. Electronic address:

Residues of the psychoactive drug diazepam (DZP) may pose potential risks to fish in aquatic environments, especially by disrupting their behavioral traits. In this study, female and male zebrafish were subjected to chronic exposure (21 days) to sublethal doses (120 and 12 µg/L) of DZP, aimed to compare the characteristics of their behavioral responses to DZP exposure, and to investigate the possible links between those behavioral responses and variations in their brain γ-aminobutyric acid (GABA) and acetylcholinesterase (AChE) levels. Chronic exposure to DZP significantly decreased the swimming velocity and locomotor activity of both genders, indicating a typical sedative effect. Read More

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January 2021

Utility of Hypertonic Saline and Diazepam in COVID-19-Related Hydroxychloroquine Toxicity.

J Emerg Med 2021 03 29;60(3):359-364. Epub 2020 Oct 29.

Harvard Medical School, Boston, Massachusetts; Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Background: Hydroxychloroquine (HCQ) poisoning is a life-threatening but treatable toxic ingestion. The scale of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) and the controversial suggestion that HCQ is a treatment option have led to a significant increase in HCQ use. HCQ poisoning should be at the top-of-mind for emergency providers in cases of toxic ingestion. Read More

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Low concentrations of oxazepam induce feeding and molecular changes in Radix balthica juveniles.

Aquat Toxicol 2021 Jan 25;230:105694. Epub 2020 Nov 25.

Biochimie et Toxicologie des Substances Bioactives, EA 7417, INU Champollion, Albi, France. Electronic address:

Psychotropics, especially benzodiazepines, are commonly prescribed worldwide. Poorly eliminated at wastewater treatment plants, they belong to a group of emerging contaminants. Due to their interaction with the GABA receptor, they may affect the function of the nervous system of non-target organisms, such as aquatic organisms. Read More

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January 2021

Up-regulation of miRNA-151-3p enhanced the neuroprotective effect of dexmedetomidine against β-amyloid by targeting DAPK-1 and TP53.

Exp Mol Pathol 2021 02 1;118:104587. Epub 2020 Dec 1.

Department of Anesthesiology, Changzhi Medical College, No.271, Taihang East Street, Changzhi City, Shanxi Province 046011, China. Electronic address:

Alzheimer's disease (AD) is the most common cause of dementia and is the leading lethal disease among the elderly. Dexmedetomidine (Dex) has been reported to have multiple neuroprotective effects, but its effect against beta-amyloid (Aβ) has not been completely determined and understood. Dex can activate both α2 adrenoceptor/cAMP/PKA and imidazoline I receptors/ERK1/2 signals. Read More

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February 2021

Oral clonazepam versus lorazepam in the treatment of methamphetamine-poisoned children: a pilot clinical trial.

BMC Pediatr 2020 12 3;20(1):543. Epub 2020 Dec 3.

Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objectives: To evaluate the efficacy of oral clonazepam versus oral lorazepam following initial parenteral benzodiazepine administration to control methamphetamine-induced agitation in children.

Methods: In a single-center clinical trial, intravenous diazepam (0.2 mg/Kg) was initially administered to all methamphetamine-poisoned pediatric patients to control their agitation, followed by a single dose of oral clonazepam (0. Read More

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December 2020

Optimized Photo-Fenton degradation of psychoactive pharmaceuticals alprazolam and diazepam using a chemometric approach-Structure and toxicity of transformation products.

J Hazard Mater 2021 02 7;403:123819. Epub 2020 Sep 7.

Environmental Pollution Control Laboratory, Chemistry Department, Aristotle University of Thessaloniki, GR-54124, Greece. Electronic address:

The objectives of the present study were: a) to evaluate the photocatalytic degradation of two benzodiazepine pharmaceuticals, alprazolam and diazepam, using Photo-Fenton, b) to optimize the experimental parameters through a central composite experimental design, c) to assess their mineralization and toxicity variations and d) to identify the transformation products during the process and to propose transformation pathways. Response Surface Methodology proved to be a useful tool for the optimization of the degradation process as the statistical coefficients (R = 0.967 for alprazolam and R = 0. Read More

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February 2021

Acute and chronic effects of diazepam on the polychaete Hediste diversicolor: Antioxidant, metabolic, pharmacologic, neurotoxic and behavioural mechanistic traits.

Environ Toxicol Pharmacol 2021 Feb 17;82:103538. Epub 2020 Nov 17.

Centro de Estudos do Ambiente e do Mar, CESAM, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal; Departamento de Biologia da Universidade de Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal. Electronic address:

Pharmaceutical drugs are widespread environmental contaminants, but data about their adverse effects are still limited to a few compounds. This study analyzed the acute (96 h) and chronic (28 days) impacts of environmentally realistic levels of diazepam (acute exposure: 0.001, 0. Read More

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February 2021

Effects of alcohol-induced increase in CYP2E1 content in human liver microsomes on the activity and cooperativity of CYP3A4.

Arch Biochem Biophys 2021 02 13;698:108677. Epub 2020 Nov 13.

Department of Chemistry, Washington State University, Pullman, WA, 99164, USA. Electronic address:

We investigate the effect of the alcohol-induced increase in the content of CYP2E1 in human liver microsomes (HLM) on the function of CYP3A4. Membrane incorporation of the purified CYP2E1 into HLM considerably increases the rate of metabolism of 7-benzyloxyquinoline (BQ) and attenuates the homotropic cooperativity observed with this CYP3A4-specific substrate. It also eliminates the activating effect of α-naphthoflavone (ANF) seen in some HLM samples. Read More

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February 2021

Repeated propofol exposure-induced neuronal damage and cognitive impairment in aged rats by activation of NF-κB pathway and NLRP3 inflammasome.

Neurosci Lett 2021 01 25;740:135461. Epub 2020 Oct 25.

Anesthesia and Operation Center, the First Medical Center, Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing 100853, China. Electronic address:

Background: Elderly patients receive propofol at regular intervals for sedation during gastrointestinal endoscopy. However, the link between cognition and intermittent propofol exposure remains unclear. Thus, we used aged rats to investigate the effect of propofol on cognition. Read More

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January 2021

Propofol Attenuates Isoflurane-Induced Neurotoxicity and Cognitive Impairment in Fetal and Offspring Mice.

Anesth Analg 2020 11;131(5):1616-1625

From the Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Anesthesia in pregnant rodents causes neurotoxicity in fetal and offspring rodents. However, the underlying mechanisms and targeted treatments remain largely to be determined. Isoflurane and propofol are among commonly used anesthetics. Read More

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November 2020

Dexmedetomidine alleviates neurobehavioral impairments and myelination deficits following lipopolysaccharide exposure in early postnatal rats.

Life Sci 2020 Dec 7;263:118556. Epub 2020 Oct 7.

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address:

Aims: White matter injury (WMI) is the main form of brain injury in preterm neonate survivors, and perinatal inflammation is implicated in the pathogenesis of WMI. It has been demonstrated that dexmedetomidine, an anesthetic adjuvant, possesses neuroprotective effects in both preclinical and clinical trials. The present study was conducted to explore whether dexmedetomidine could protect against neurobehavioral impairments and myelination deficits caused by lipopolysaccharide (LPS) exposure in the early postnatal rat brain. Read More

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December 2020

Toxicological outcome of exposure to psychoactive drugs carbamazepine and diazepam on non-target insect Nauphoeta cinerea.

Chemosphere 2021 Feb 28;264(Pt 1):128449. Epub 2020 Sep 28.

Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.

The continuous detection of human pharmaceuticals during environmental biomonitoring is a global concern because of the menaces they may exert on non-target organisms. Carbamazepine (CBZ) and diazepam (DZP) are commonly prescribed psychotropic drugs which have been reported to coexist in the environment globally. Nauphoeta cinerea is a common insect with high ecological impact. Read More

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February 2021

Design, synthesis, and pharmacological evaluation of novel 1,2,4-triazol-3-amine derivatives as potential agonists of GABA subtype receptors with anticonvulsant and hypnotic effects.

Bioorg Chem 2020 11 1;104:104212. Epub 2020 Sep 1.

Department of Pharmacology and Toxicology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran. Electronic address:

In the current study, a series of novel 1,2,4-triazol-3-amine derivatives were designed, synthesized, and biologically evaluated in vivo for their anticonvulsant and hypnotic effects in the pentylenetetrazole (PTZ)-induced seizures, maximal electroshock (MES)-induced seizures, and pentobarbital-induced sleeping tests. Furthermore, the possible side effects of the most potent compounds on the memory, motor coordination, and muscle strength were evaluated in passive avoidance, rotarod, and grip strength tests, respectively. The designed compounds with the main benzodiazepine pharmacophores including aromatic ring and proton accepting group completely mimiced the structure of zolpidem as an α1-selective agonist of GABA receptor. Read More

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November 2020

A simplified and sensitive LC-APCI-MS/MS method for the quantification of propofol: Application to a bioequivalence study in healthy Chinese subjects.

Int J Clin Pharmacol Ther 2020 Nov;58(11):664-674

Objectives: Propofol has become the preferred anesthetic in recent years due to its desirable pharmacologic properties. However, propofol possesses a very narrow therapeutic window between the favorable clinical effect and potentially lethal toxicity, therefore, a rapid, simplified, and sensitive liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) method is presented in this study for the quantification of propofol in human plasma using the isotope-labeled internal standard (IS) of propofol-d17, and then applied in a bioequivalence study.

Materials And Methods: Sample preparation was accomplished through simple one-step precipitation of plasma protein with acetonitrile. Read More

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November 2020

Flubromazolam: Detection in five post-mortem cases.

Med Sci Law 2020 Oct 24;60(4):266-269. Epub 2020 Aug 24.

Forensic Toxicology Service, University Hospitals of Leicester NHS Trust, UK.

Flubromazolam is a potent triazole benzodiazepine with moderately long-lasting central nervous system-depressant effects relative to other benzodiazepines such as commonly prescribed diazepam. Flubromazolam has been studied in the living. However, there are no published reports including measured drug concentrations in post-mortem cases. Read More

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October 2020

Transformation of diazepam in water during UV/chlorine and simulated sunlight/chlorine advanced oxidation processes.

Sci Total Environ 2020 Dec 28;746:141332. Epub 2020 Jul 28.

SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, Guangzhou 510006, China.

Psychoactive drug diazepam is one of benzodiazepines widely used in human medicine. It has been found to be relatively resistant to chlorination and photolysis. Here we investigated the transformation mechanism of diazepam in aqueous solution through UV/chlorine and simulated sunlight/chlorine treatments. Read More

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December 2020