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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

Radiol Case Rep 2021 May 20;16(5):1207-1210. Epub 2021 Mar 20.

Division of Neuroradiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

In the midst of the national opioid crisis, it is necessary for emergency physicians and radiologists to be familiar with presentations of opioid-related complications. We describe a case report of a 51-year-old female who developed bilateral cerebellar hemorrhages following opioid and benzodiazepine overdose. Malignant cerebellar edema is a rare but recognized complication following opiate overdose in children or chronic heroin toxicity. Read More

Clin Toxicol (Phila) 2021 Jun 23;59(6):451-456. Epub 2021 Mar 23.

New Mexico Poison and Drug Information Center, Albuquerque, NM, USA.

Background: Seizures are a common manifestation of toxic exposures requiring immediate and possibly ongoing management. Guidelines recommend benzodiazepines as first-line therapy for toxic seizures; however, there is a paucity of literature regarding optimal secondary treatment. We systematically evaluated the available literature for second-line treatment of toxic seizures. Read More

Neurochem Int 2021 Jun 16;146:105021. Epub 2021 Mar 16.

Department of Organic and Inorganic Chemistry, Science Center, Federal University of Ceará, Fortaleza, CE, 60455-760, Brazil. Electronic address:

Benzodiazepines are commonly used to treat disorders of the central nervous system, including anxiety. However, due to their adverse effects, there is a continuing interest in discovering new safe and effective drugs. Marine natural products have emerged as a prolific source of bioactive nitrogenated compounds. Read More

Addiction 2021 Mar 19. Epub 2021 Mar 19.

European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon, Portugal.

Aims: To determine trends in 3,4 methylenedioxymethamphetamine (MDMA)-related death rates across Australia, Finland, Portugal and Turkey and to analyse the toxicology and causes of death across countries.

Design: Analysis of MDMA-related deaths extracted from a national coronial database in Australia (2001-19) and national forensic toxicology databases in Finland (2001-17), Portugal (2008-19) and Turkey (2007-17). Presentation of MDMA use and seizure data (market indicators). Read More

Aust N Z J Psychiatry 2021 Mar 18:4867421998788. Epub 2021 Mar 18.

Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.

Objective: Concerns about intentional and unintentional poisoning present a barrier to wider use of clozapine in treatment-resistant schizophrenia. The objective of this study was to investigate decedent demographics and trends in fatal poisonings in Australia involving clozapine.

Methods: This was a retrospective case series of all fatal drug toxicity reported to an Australian coroner between 1 May 2000 and 31 December 2016 where toxicological analysis detected clozapine. Read More

Clin Toxicol (Phila) 2021 Mar 16:1-13. Epub 2021 Mar 16.

Emergency Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.

Objective: To analyse the relative percentage of acute recreational drug toxicity emergency department (ED) presentations involving the main drug groups according to age and sex and investigate different patterns based on sex and age strata.

Methods: We analysed all patients with acute recreational drug toxicity included by the Euro-DEN Plus dataset (22 EDs in 14 European countries) between October 2013 and December 2016 (39 months). Drugs were grouped as: opioids, cocaine, cannabis, amphetamines, gamma-hydroxybutyrate (GHB), hallucinogens, new psychoactive substances (NPS), benzodiazepines and ketamine. Read More

Epilepsy Behav 2021 04 9;117:107881. Epub 2021 Mar 9.

State University of Ceará, Graduate Program in Natural Sciences, Natural Products Chemistry Laboratory, Fortaleza, Ceará, Brazil; Postgraduate Program in Biological Chemistry, Department of Biological Chemistry, Regional University of Cariri, Crato, Ceará, Brazil; Center for Exact Sciences and Technology, Vale do Acaraú State University, Sobral, Ceará, Brazil. Electronic address:

In the treatment of anxiety and seizures, drugs of the benzodiazepine (BZD) class are used, which act on the Central Nervous System (CNS) through the neurotransmitter gamma-aminobutyric acid (GABA). Flavonoids modulate GABAA receptors. The aim of this study was to evaluate the anxiolytic and anticonvulsant effects of synthetic chalcones and their mechanisms of action via the GABAergic system, using adult zebrafish (ZFa). Read More

Eur J Pharm Sci 2021 Jun 8;161:105792. Epub 2021 Mar 8.

Southern Federal University, Research Institute of Physical and Organic Chemistry; 105/42 Bolshaya Sadovaya str., Rostov-on-Don, Russia.

A study on the anxiolytic activity of the new derivatives of 11-dialkylaminoethyl-2,3,4,5-tetrahydrodiazepino[1,2-a]benzimidazole, containing privileged scaffolds of benzodiazepine and benzimidazole in their structure, was conducted. The cytotoxic properties of low levels of six compounds were preliminary determined in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. The screening of these substances for anxiolytic activity was conducted using elevated plus maze (EPM) test in vivo, and DAB-21 was found to be the most active compound. Read More

Environ Pollut 2021 Jun 24;278:116777. Epub 2021 Feb 24.

Department of Biology, Murray State University, Murray, KY, United States.

A recent surge in the use and abuse of diverse prescribed psychotic and illicit drugs necessitates the surveillance of drug residues in source water and the associated ecological impacts of chronic exposure to the aquatic organism. Thirty-six psychotic and illicit drug residues were determined in discharged wastewater from two centralized municipal wastewater treatment facilities and two wastewater receiving creeks for seven consecutive days in Kentucky. Zebrafish (Danio rerio) larvae were exposed to the environmental relevant mixtures of all drug residues, all illicit drugs, and all prescribed psychotic drugs. Read More

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

Eur J Clin Pharmacol 2021 Apr;77(4):555-556

Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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

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

BMJ Open 2020 11 20;10(11):e038692. Epub 2020 Nov 20.

School of Public Health, University of Alberta, Edmonton, Alberta, Canada

Objectives: Coprescribing of benzodiazepines/Z-drugs (BZDs) and opioids is a drug-use pattern of considerable concern due to risk of adverse events. The objective of this study is to estimate the effect of concurrent use of BZDs on the risk of hospitalisations/emergency department (ED) visits and deaths among opioid users.

Design, Setting And Participants: We conducted a population-based case cross-over study during 2016-2018 involving Albertans 18 years of age and over who received opioids. Read More

J Med Toxicol 2021 Apr 13;17(2):168-175. Epub 2021 Jan 13.

Department of Medical Toxicology, Banner - University Medical Center Phoenix, 1012 E Willetta St., 2nd floor, Phoenix, AZ, 85006, USA.

Introduction: Methamphetamine toxicity is common in the Southwest region of the United States and presents diagnostic and treatment challenges in the pediatric population. The aim of our study was to characterize signs and symptoms of methamphetamine toxicity in pediatric patients, highlighting manifestations unique to this population. Additionally, our study sought to evaluate treatment modalities, specifically antipsychotics, in this population with the intent to characterize their adverse effects. Read More

Ther Adv Psychopharmacol 2020 17;10:2045125320967197. Epub 2020 Dec 17.

Consultant Psychiatrist, Oxleas NHS Foundation Trust, London, UK.

New psychoactive substances (NPS) are a heterogeneous group of substances. They are associated with a number of health and social harms on an individual and societal level. NPS toxicity and dependence syndromes are recognised in primary care, emergency departments, psychiatric inpatient and community care settings. Read More

Mayo Clin Proc 2021 01;96(1):242-256

Division of Community Internal Medicine, Mayo Clinic, Rochester, MN.

Medications to treat disease and extend life in our patients often amass in quantities, resulting in what has been termed "polypharmacy." This imprecise label usually describes the accumulation of 5, and often more, medications. Polypharmacy in advancing age frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and nonadherence. Read More

Neurotherapeutics 2021 01 6;18(1):544-555. Epub 2021 Jan 6.

Department of Neurology, School of Medicine, University of California, Davis, Sacramento, CA, 95817, USA.

Allopregnanolone, a positive modulator of GABA receptors with antiseizure activity, has potential in the treatment of seizure emergencies. Instillation of allopregnanolone in 40% sulfobutylether-β-cyclodextrin into the nose in mice rapidly elevated the seizure threshold in the timed intravenous pentylenetetrazol (ED, 5.6 mg/kg), picrotoxin (ED, 5. Read More

Environ Sci Pollut Res Int 2021 Jan 4. Epub 2021 Jan 4.

CIEPQPF - Research Centre of Chemical Process Engineering and Forest Products, Department of Chemical Engineering, University of Coimbra, P-3030-790, Coimbra, Portugal.

Contaminants of emerging concern (CECs) are released daily into surface water, and their recalcitrant properties often require tertiary treatment. Electrochemical oxidation (EO) is often used as an alternative way to eliminate these compounds from water, although the literature barely addresses the neurotoxic effects of residual by-products. Therefore, this study investigated the performance of EO in the removal of five CECs (alprazolam, clonazepam, diazepam, lorazepam, and carbamazepine) and performed neurotoxicity evaluations of residual EO by-products in Wistar rat brain hippocampal slices. Read More

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

Neurobiol Dis 2021 02 29;149:105245. Epub 2020 Dec 29.

Department of Neurology, University of Wisconsin, School of Medicine, Madison, WI, USA. Electronic address:

Barbiturates and benzodiazepines are potent GABA receptor agonists and strong anticonvulsants. In the developing brain they can cause neuronal and oligodendroglia apoptosis, impair synaptogenesis, inhibit neurogenesis and trigger long-term neurocognitive sequelae. In humans, the vulnerable period is projected to extend from the third trimester of pregnancy to the third year of life. Read More

Neuropharmacology 2021 03 5;185:108444. Epub 2021 Jan 5.

Department of Neurology, David Geffen School of Medicine at UCLA, Epilepsy Research Laboratory (151), Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.

The initiation and maintenance of cholinergic-induced status epilepticus (SE) are associated with decreased synaptic gamma-aminobutyric acid A receptors (GABAR) and increased N-methyl-d-aspartate receptors (NMDAR) and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). We hypothesized that trafficking of synaptic GABAR and glutamate receptors is maladaptive and contributes to the pharmacoresistance to antiseizure drugs; targeting these components should ameliorate the pathophysiological consequences of refractory SE (RSE). We review studies of rodent models of cholinergic-induced SE, in which we used a benzodiazepine allosteric GABAR modulator to correct loss of inhibition, concurrent with the NMDA antagonist ketamine to reduce excitation caused by increased synaptic localization of NMDAR and AMPAR, which are NMDAR-dependent. Read More

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

Addict Behav 2021 03 4;114:106752. Epub 2020 Dec 4.

West Virginia University School of Medicine (WVU SOM), Morgantown, WV 26505, USA; West Virginia Clinical and Translational Science Institute, Morgantown, WV 26505, USA.

Objective: Funding to address the current opioid epidemic has focused on treatment of opioid use disorder (OUD); however, rates of other substance use disorders (SUDs) remain high and non-opioid related overdoses account for nearly 30% of overdoses. This study assesses the prevalence of co-occurring substance use in West Virginia (WV) to inform treatment strategies. The objective of this study was to assess the prevalence of, and demographic and clinical characteristics (including age, gender, hepatitis C virus (HCV) status) associated with, co-occurring substance use among patients with OUD in WV. Read More

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

Int J Mol Sci 2020 Dec 8;21(24). Epub 2020 Dec 8.

Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA.

Patients with severe mental illness have increased mortality, often linked to cardio-metabolic disease. Non-alcoholic fatty liver disease (NAFLD) incidence is higher in patients with schizophrenia and is exacerbated with antipsychotic treatment. NAFLD is associated with obesity and insulin resistance, both of which are induced by several antipsychotic medications. Read More

Clin Toxicol (Phila) 2020 Dec 9:1-13. Epub 2020 Dec 9.

Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, University of Colorado Hospital, Aurora, CO, USA.

Background: Toxicity from antimuscarinic agents precipitates a constellation of signs and symptoms; two of the most significant are agitation and delirium. Benzodiazepines are commonly used for treatment; physostigmine is also effective but is underutilized due to concerns for safety and short duration of action. The objective of this study was to compare lorazepam to physostigmine for the treatment of antimuscarinic delirium and agitation. Read More

Neurotoxicology 2021 01 5;82:130-136. Epub 2020 Dec 5.

US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, United States. Electronic address:

Cannabidiol, approved for treatment of pediatric refractory epilepsy, has anti-seizure effects in various animal seizure models. Chemical warfare nerve agents, including soman, are organophosphorus chemicals that can induce seizure and death if untreated or if treatment is delayed. Our objective was to evaluate whether cannabidiol would ameliorate soman-induced toxicity using a mouse model that similar to humans lacks plasma carboxylesterase. Read More