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Drug Dev Res 2019 Apr 11. Epub 2019 Apr 11.

Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hacettepe University, Ankara, Turkey.

An estimated 50 million people suffer epilepsy worldwide and 30% of the cases do not respond to current antiepileptic drugs (AEDs). Here, we report synthesis and anticonvulsant screening of new derivatives of nafimidone, a well-known member of (arylakyl)azole anticonvulsants. The compounds showed promising protection against maximal electroshock (MES)-induced seizures in mice and rats when administered via intraperitoneal (ip) and oral route. Read More

Behav Brain Res 2019 Mar 25. Epub 2019 Mar 25.

State University of Ceará, Science and Technology Center (CCT), Itaperi Campus, Laboratory of Natural Products Chemistry - LQPN-S, CEP 60741-000, Fortaleza, Ceará, Brazil. Electronic address:

Benzodiazepines are the standard drugs for the treatment of anxiety, but their undesirable side effects make it necessary to develop new anxiolytic drugs. The objective of this study was to evaluate the possible anxiolytic-simile effect of synthetic chalcone N-{(4'-[(E)-3-(4-fluorophenyl)-1-(phenyl) prop-2-en-1-one]} acetamide (PAAPFBA) on adult zebrafish (Danio rerio). PAAPFBA was synthesized with an 88. Read More

Med Pr 2019 Apr 19;70(2):229-247. Epub 2019 Mar 19.

Uniwersytet Medyczny w Łodzi / Medical University of Lodz, Łódź, Poland (Zakład Toksykologii, Międzywydziałowa Katedra Farmakologii Ogólnej, Klinicznej i Toksykologii / Department of Toxicology, Interdepartmental Chair of General and Clinical Pharmacology and Toxicology).

Background: Stress is a result of disturbed homeostasis and can contribute to the development of many diseases. One of the methods of combating stress is aromatherapy, which uses essential oils with a calming and relaxing effect. The aim of the work was to perform a qualitative analysis of selected essential oils with a relaxing effect. Read More

Neurotoxicology 2019 Feb 23;73:8-16. Epub 2019 Feb 23.

Department of Pharmacodynamics, Medical University of Łódź, 90-151 Łódź, Muszynskiego 1, Poland.

The abuse of new psychoactive substances (NPS) has been increasing dramatically since the late 2000s worldwide. Between 2009 and 2017, a total of 803 individual NPS were reported to the United Nations Office of Drugs and Crime by 111 countries and territories. Although the most popular compounds are synthetic cannabinomimetics and psychostimulatory derivatives of cathinone (so-called β-keto-amphetamines), novel benzodiazepines have recently emerged on the recreational drug market. Read More

J Med Chem 2019 Mar 26;62(5):2666-2689. Epub 2019 Feb 26.

Department of Molecular and Cellular Oncology , The University of Texas MD Anderson Cancer Center , Houston , Texas 77030 , United States.

Since the discovery of compound BIX01294 over 10 years ago, only a very limited number of nonquinazoline inhibitors of H3K9-specific methyltransferases G9a and G9a-like protein (GLP) have been reported. Herein, we report the identification of a novel chemotype for G9a/GLP inhibitors, based on the underinvestigated 2-alkyl-5-amino- and 2-aryl-5-amino-substituted 3 H-benzo[ e][1,4]diazepine scaffold. Our research efforts resulted in the identification 12a (EML741), which not only maintained the high in vitro and cellular potency of its quinazoline counterpart, but also displayed improved inhibitory potency against DNA methyltransferase 1, improved selectivity against other methyltransferases, low cell toxicity, and improved apparent permeability values in both parallel artificial membrane permeability assay (PAMPA) and blood-brain barrier-specific PAMPA, and therefore might potentially be a better candidate for animal studies. Read More

J Clin Neurophysiol 2019 Jan 24. Epub 2019 Jan 24.

Department of Neurology, Royal Perth Hospital, Perth, Australia.

Purpose: Baclofen has been reported to cause both a metabolic encephalopathy and nonconvulsive status epilepticus. Baclofen is typically used in the management of muscle spasticity but is being increasingly used to manage alcohol withdrawal and opiate dependency. Given the increasing use of baclofen we describe the clinical and electrographical features of baclofen neurotoxicity seen at our institution. Read More

Ecotoxicol Environ Saf 2019 Apr 17;171:781-789. Epub 2019 Jan 17.

Fiocruz, Departamento de Saneamento e Saúde Ambiental, Escola Nacional de Saúde Pública (ENSP), Av. Brasil, 4.365, Manguinhos, 21040-360 Rio de Janeiro, RJ, Brazil. Electronic address:

Contaminants of emerging concern have become an important environmental problem, especially pharmaceutically active compounds (PhACs), since, after use, these drugs return to the environment, contaminating aquatic ecosystems. Some may display the ability to bioaccumulate and biomagnify throughout the food chain, leading to potential environmental and human deleterious effects which are, however, still largely unknown. In this context, the aim of the present study was to evaluate the effect of two psychotropic drugs commonly found in the environment, carbamazepine (CBZ) and clonazepam (CZP), both isolated and co-administrated, on oxidative stress biomarkers and essential metal homeostasis in Danio rerio fish specimens. Read More

Am J Emerg Med 2019 Jan 6. Epub 2019 Jan 6.

Department of Emergency Medicine, McGill University Health Centre, Montréal, Québec, Canada; Centre Antipoison Du Québec, Montréal, Québec, Canada; Département d'urgence, Hôpital Charles-Lemoyne, Greenfield Park, Qc, Canada.

Objective: Benzodiazepines are often recommended first-line for management of cocaine and amphetamine toxicity while antipsychotic treatment is discouraged due to the potential for lowering seizure threshold, prolonging the QT interval, and decreasing heat dissipation. We performed a systematic review including animal and human studies to elucidate the efficacy and safety of antipsychotics in managing sympathomimetic toxicity specifically evaluating the effect of treatment on mortality, seizures, hyperthermia, and cardiovascular effects.

Methods: We searched MEDLINE, Embase, BIOSIS Previews, Web of Science, Scopus, CENTRAL and gray literature from inception to 31 May 2017 to answer: Can antipsychotics be used safely and effectively to treat cocaine or amphetamine toxicity? Citations were screened by title and abstract. Read More

Int J Geriatr Psychiatry 2019 Jan 4. Epub 2019 Jan 4.

Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan.

Objective: Pyrus pashia has traditionally been used as a therapeutic agent including sedative. In this regard, hydroethanolic extract of Pyrus pashia (HEPP) was screened for phytochemical investigation, acute toxicity, and sedative-hypnotic activity to provide a scientific rationale to its ethno-medicinal uses.

Methods: Mice were used in acute toxicity test; sedative potential was observed in open field test while thiopental-induced sleeping time and barbiturate-induced sleeping time tests were used for the assessment of hypnotic like effects of HEPP. Read More

AAPS PharmSciTech 2019 Jan 2;20(1):22. Epub 2019 Jan 2.

Department of Pharmaceutics, Sinhgad Institute of Pharmacy, Sinhgad Technical Education Society, Narhe, Pune, MS, 411041, India.

Potential risk of agranulocytosis is one of the drug-induced adverse effects of the second-generation antipsychotic agents. The present investigation aimed to formulate and investigate olanzapine (OLZ)-loaded nanostructured lipid carriers (OLZ-NLCs) via intranasal (i.n. Read More

Aquat Toxicol 2019 Feb 1;207:170-178. Epub 2018 Dec 1.

Department of Ecology and Environmental Science, Umeå University, SE-90187, Umeå, Sweden; Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, SE-90183, Umeå, Sweden.

Pharmaceuticals entering aquatic ecosystems via wastewater effluents are of increasing concern for wild animals. Because some pharmaceuticals are designed to modulate human behaviour, measuring the impacts of exposure to pharmaceuticals on fish behaviour has become a valuable endpoint. While laboratory studies have shown that pharmaceuticals can affect fish behaviour, there is a lack of understanding if behaviour is similarly affected in natural environments. Read More

Cochrane Database Syst Rev 2018 12 19;12:CD013230. Epub 2018 Dec 19.

Centre for Evidence-Based Practice (CEBaP), Belgian Red Cross, Motstraat 42, Mechelen, Belgium, 2800.

Background: Oral poisoning is a major cause of mortality and disability worldwide, with estimates of over 100,000 deaths due to unintentional poisoning each year and an overrepresentation of children below five years of age. Any effective intervention that laypeople can apply to limit or delay uptake or to evacuate, dilute or neutralize the poison before professional help arrives may limit toxicity and save lives.

Objectives: To assess the effects of pre-hospital interventions (alone or in combination) for treating acute oral poisoning, available to and feasible for laypeople before the arrival of professional help. Read More

Drug Discov Today Technol 2018 Dec 6;30:71-83. Epub 2018 Dec 6.

Femtogenix Ltd., Biopark, Broadwater Road, Welwyn Garden City AL7 3AX, United Kingdom; Institute for Pharmaceutical Science, King's College London, Faculty of Life Sciences and Medicine, Franklin Wilkins Building, London SE1 9NH, United Kingdom. Electronic address:

Antibody-drug conjugates (ADCs) consist of monoclonal antibodies (mAbs) or antibody fragments conjugated to biologically active molecules (usually highly cytotoxic small molecules) through chemical linkers. Although no ADCs containing covalent-binding DNA-interactive payloads have yet been approved (although two containing the DNA-cleaving payload calicheamicin have), of those in clinical trials systemic toxicities are beginning to emerge. This article discusses the observed toxicities in relation to the structures and mechanisms of action of payload type. Read More

Am J Emerg Med 2019 Mar 26;37(3):562.e5-562.e10. Epub 2018 Nov 26.

Department of Emergency Medicine, Jacobi Medical Center, Bronx, NY, United States of America.

A 27-year-old man presented with an intentional overdose of concentrated caffeine powder that he bought over the internet. The patient received benzodiazepines and ondansetron for symptomatic treatment when he arrived in the Emergency Department (ED). Subsequently, he developed recurrent supraventricular tachycardia in the ED. Read More

Chemosphere 2019 Mar 15;218:223-231. Epub 2018 Nov 15.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China; Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing, 100013, China. Electronic address:

Diazepam (DZP) is often found in source water and drinking water at dozens of nanograms per liter levels. The transformation of DZP in water chlorination disinfection process has aroused new concern because the toxic disinfection byproducts (DBPs) might be produced. However, the DBPs of DZP have not been fully identified, and their occurrence levels in drinking water have not been reported. Read More

Neurobiol Dis 2018 Nov 20. Epub 2018 Nov 20.

National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States.

This special issue will describe cutting-edge translational research on the development of safe and effective therapeutics for treating exposure to toxic chemical threat agents that target the nervous system. These studies are supported by the National Institutes of Health (NIH) Countermeasures Against Chemical Threats (CounterACT) program. Chemical threats include chemical warfare agents, pesticides and other toxic chemicals whose primary mode of action is targeted within the nervous system. Read More

J Pharm Biomed Anal 2019 Feb 28;164:430-441. Epub 2018 Oct 28.

School of Pharmaceutical Sciences of Ribeirão Preto, Department of Clinical Analysis, Toxicology and Food Science, University of São Paulo, Brazil; Ribeirão Preto Medical School, Department of Internal Medicine, University of São Paulo, Brazil. Electronic address:

Drug transporters and CYP enzymes are important sources of pharmacokinetics (PK) variability in drug responses and can cause various pharmacological and toxicological consequences, leading to either toxicity or an insufficient pharmacological effect. In recent years, the cocktail approach was developed to determine in vivo CYP and transporters activities, but these approaches are somewhat limited. We described the development and validation of three sensitive and specific LC-MS/MS assays for the determination of P-gp and major human CYP isoenzyme activities following oral administration of a drug cocktail of subtherapeutic doses (lower than 10 times) of caffeine (CAF), omeprazole (OME), losartan (LOS), midazolam (MDZ), metoprolol (METO) and fexofenadine (FEX) in healthy volunteers. Read More

J Emerg Trauma Shock 2018 Jul-Sep;11(3):228-229

Department of Emergency Medicine and Critical Care, Amrita University, Kochi, Kerala, India.

Camphor is a toxic compound easily available over the counter, which can cause fatal seizures in children when ingested. It is available in several forms and is commonly used in Indian households, especially for religious rituals and for its cough-suppressive and nasal-decongestant effect. The toxic effect remains unknown in most homes. Read More

J Anesth 2019 Feb 11;33(1):1-8. Epub 2018 Nov 11.

Systemic toxicity from local anesthetics can occur in any of the wide range of situations in which these agents are used. This practical guide is created to generate a shared awareness of the prevention, diagnosis, and treatment of local anesthetic systemic toxicity among all medical professionals who perform nerve blocks. Systemic toxicity of local anesthetic is induced by an increase of its protein-unbound plasma concentration. Read More

J Alzheimers Dis 2018 ;66(3):935-938

Department of Neurology, University of Louisville, Louisville, KY, USA.

The toxicity associated with long-standing benzodiazepine use in older persons is a critical issue. Several epidemiological reports have studied correlation between benzodiazepine use and risk of dementia development. In this manuscript, we used a case report to demonstrate how chronic diazepam use can cause cognitive deficits that resemble Alzheimer's disease and related conditions. Read More

Curr Drug Discov Technol 2018 Nov 4. Epub 2018 Nov 4.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad. Iran.

Background: Insomnia is the most common sleep disorder. The present study was undertaken to evaluate the sedative-hypnotic potential of hydroalcoholic extract (HAE) of Cuscuta epithymum and its fractions.

Method: HAE and its fractions including: water fraction (WF), ethyl acetate fraction (EAF) and n-hexan fraction (NHF) were i. Read More

BMJ Case Rep 2018 Oct 30;2018. Epub 2018 Oct 30.

College of Pharmacy, University of Florida, Gainesville, Florida, USA.

We report a case of a hospitalised patient who developed probable serotonin toxicity shortly after the initiation of linezolid in whom the selective serotonin reuptake inhibitor (SSRI) escitalopram had been recently discontinued. On day 2 of linezolid administration, the patient reported severe anxiety and was observed to have full body jerking and twitching motions without mental status change. Notably, the patient was concomitantly receiving the antidepressant, trazodone and the benzodiazepine, clonazepam possibly affecting the severity and manifestations of serotonin toxicity. Read More

Epilepsia 2018 12 25;59(12):2206-2218. Epub 2018 Oct 25.

US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.

Objective: Exposure to chemical warfare nerve agents (CWNAs), such as soman (GD), can induce status epilepticus (SE) that becomes refractory to benzodiazepines when treatment is delayed, leading to increased risk of epileptogenesis, severe neuropathology, and long-term behavioral and cognitive deficits. Rodent models, widely used to evaluate novel medical countermeasures (MCMs) against CWNA exposure, normally express plasma carboxylesterase, an enzyme involved in the metabolism of certain organophosphorus compounds. To better predict the efficacy of novel MCMs against CWNA exposure in human casualties, it is crucial to use appropriate animal models that mirror the human condition. Read More

Neurosci Lett 2019 01 7;690:29-35. Epub 2018 Oct 7.

Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, La Habana, Cuba. Electronic address:

Oxidative stress and mitochondrial dysfunction are two pathophysiological factors often associated with the neurodegenerative process involved in Parkinson's disease (PD). The aim of this study was to investigate the effects of a novel hybrid molecule, named JM-20, in different in vitro and in vivo models of PD induced by rotenone. To perform in vitro studies, SHSY-5Y cells were exposed to rotenone and/or treated with JM-20. Read More

Eur J Clin Pharmacol 2019 Jan 22;75(1):77-85. Epub 2018 Sep 22.

Clinical Toxicology, Guy's and St Thomas' Hospitals NHS Foundation Trust, and King's Health Partners, London, UK.

Background: Non-medical use of benzodiazepines and Z-drugs is common; however, there is limited information available on the extent of harm related to this in Europe, as well as the relationship between misuse and availability.

Aim: To describe presentations to the emergency department in Europe related to the recreational use of benzodiazepines and Z-drugs and compare regional differences in these presentations with legal drug sales of benzodiazepines and Z-drugs within each country.

Methods: Emergency department presentations with recreational misuse of benzodiazepines and Z-drugs were obtained from the Euro-DEN dataset for the period from October 2013 to September 2015; data extracted included demographics, clinical features, reported coused drugs, and outcome data. Read More

Bioorg Med Chem 2018 10 11;26(18):5151-5158. Epub 2018 Sep 11.

Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China. Electronic address:

Cadmium (Cd) is a potent toxic heavy metal, some studies showed that Cd-induced apoptosis is through ER stress pathway. Compounds of pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-3,11-diones were discovered as potent neuroprotective agents against Cd-induced toxicity in SH-SY5Y cells for the first time. In this study, twenty-six PBD-3,11-dione derivatives were synthesized and evaluated for their neuroprotective activity against Cd-induced toxicity by CCK-8 assay. Read More

Medicine (Baltimore) 2018 Sep;97(38):e12454

Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Rationale: Anesthesiologists have a well-known increased risk of substance abuse. High-concentration of inhalation anesthetics in exhaled air of operating room personnel is detected. such secondhand exposure produces neurobiological sensitization to the reinforcing effects of inhalation anesthetics. Read More

Am J Ther 2018 Sep/Oct;25(5):e601-e602

Hepatology Unit, Universitat Autònoma de Barcelona, Barcelona, Spain.

Drug Metab Dispos 2018 11 30;46(11):1507-1513. Epub 2018 Aug 30.

Departments of Microbiology and Immunology (T.V., H.d.J., H.d.L., D.R.J.K.), Pharmaceutical and Pharmacological Sciences (J.d.H.), and Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences (M.O., P.A.), Catholic University of Leuven, Leuven, Belgium; Department of Nephrology and Renal Transplantation (T.V., H.d.J., H.d.L., D.R.J.K.), and Center for Clinical Pharmacology (J.d.H.), University Hospitals Leuven, Leuven, Belgium; Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden; (A.P.); and Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden (A.P.)

CYP3A5 genotype is a major determinant of tacrolimus clearance, and has been shown to affect systemic tacrolimus metabolite/parent ratios in healthy volunteers, which may have implications for efficacy and toxicity. In a cohort of 50 renal transplant recipients who underwent quantification of CYP3A4 activity using the oral midazolam drug probe, we confirmed that CYP3A5 genotype is the single most important determinant of tacrolimus metabolite/parent ratio [CYP3A5 expressors displayed 2.7- and 2-fold higher relative exposure to 13-desmethyltacrolimus (DMT) and 31-DMT, respectively; < 0. Read More

Toxicol Lett 2018 Nov 27;297:19-23. Epub 2018 Aug 27.

Experimental Anesthesiology Section, Department of Anesthesiology and Intensive Care Medicine, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany. Electronic address:

Intoxication with organophosphorus compounds can result in life-threatening organ dysfunction and refractory seizures. Sedation or hypnosis is essential to facilitate mechanical ventilation and control seizure activity. The range of indications for midazolam includes both hypnosis and seizure control. Read More

Epilepsia 2018 10 29;59 Suppl 2:92-99. Epub 2018 Aug 29.

Department of Neurology and Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Nerve agents are organophosphate (OP) compounds and among the most powerful poisons known to man. A terrorist attack on civilian or military populations causing mass casualties is a real threat. The OP nerve agents include soman, sarin, cyclosarin, tabun, and VX. Read More

Ann Transplant 2018 Aug 28;23:608-614. Epub 2018 Aug 28.

Department of Surgery, Division of Abdominal Transplant, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.

BACKGROUND Central nervous system complications after transplantation occur in up to 40% of recipients and these complications are associated with increased length of hospital stay and mortality. Catatonia is a neuropsychiatric clinical syndrome which has been described in case reports and in a small case series as occurring in the immediate post-solid organ transplantation (SOT) period, and it has been attributed to calcineurin inhibitor neurotoxicity, psychological vulnerability, and depression. Among transplant recipients, the incidence of catatonia is unknown; it may be under diagnosed in part due to a broad differential diagnosis in the post-transplantation setting, which includes hypoactive delirium, non-convulsive status epilepticus, drug toxicity, conversion disorder, and volitional uncooperativeness. Read More

Neurotoxicology 2018 09 18;68:167-176. Epub 2018 Aug 18.

CBRN Protection, TNO Defense, Safety and Security, Rijswijk, PO Box 2280 AA, The Netherlands. Electronic address:

Organophosphate (OP) induced seizures are commonly treated with anticholinergics, oximes and anticonvulsants. Inhibition of P-glycoprotein (PgP) has been shown to enhance the efficacy of nerve agent treatment in soman exposed rats. In the present study, the promising effects of the PgP inhibitor tariquidar were investigated in more detail in rats s. Read More

Drug Test Anal 2019 Feb 5;11(2):223-229. Epub 2018 Sep 5.

Institut de médecine légale, Strasbourg, France.

Designer benzodiazepines have emerged as recreational drugs. They are available via the Internet without control and are found in the form of falsified (fake) medicines. For some of them, limited information concerning their effects, their toxicity, and their detection in bio fluids is available in the literature. Read More

Drug Alcohol Depend 2018 10 31;191:86-90. Epub 2018 Jul 31.

Institute for Clinical Evaluative Sciences, 2075 Bayview Ave, Toronto, Ontario M4N 3M5, Canada; Department of Medicine at the University of Toronto, 1 King's College Circle, Medical Sciences Building, Toronto, Ontario M5S 1A8, Canada.

Background: The Canadian opioid crisis is a complex, multifaceted problem involving prescribed, diverted and illicitly manufactured opioids. This study sought to characterize the contribution of prescribed opioids to opioid-related hospitalizations in Canada.

Methods: We conducted a cross-sectional study of all individuals who were admitted to hospital for opioid toxicity in British Columbia (BC), Manitoba and Ontario between April 2015 and March 2016. Read More

Res Social Adm Pharm 2018 Jul 3. Epub 2018 Jul 3.

Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia; School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.

Background: Evidence is accumulating globally on harms from extramedical prescription opioid analgesic (POA) use.

Objective: The aim of this scoping review was to explore harms and documented risk factors associated with extramedical POA use in Australia.

Methods: MEDLINE, EMBASE, PsycINFO and CINAHL were searched for original studies published between January 2000 and February 2018. Read More

Clin Toxicol (Phila) 2019 Feb 3;57(2):99-103. Epub 2018 Aug 3.

a Department of Emergency Medicine , Oregon Health and Science University , Portland , OR , USA.

Background: Amanita muscaria (AM) and A. pantherina (AP) contain ibotenic acid and muscimol and may cause both excitatory and sedating symptoms. Gastrointestinal (GI) symptoms are not classically described but have been reported. Read More

MMWR Morb Mortal Wkly Rep 2018 Aug 3;67(30):815-818. Epub 2018 Aug 3.

Tianeptine (marketed as Coaxil or Stablon) is an atypical tricyclic drug used as an antidepressant in Europe, Asia, and Latin America. In the United States, tianeptine is not approved by the Food and Drug Administration (FDA) for medical use and is an unscheduled pharmaceutical agent* (1). Animal and human studies show that tianeptine is an opioid receptor agonist (2). Read More

J Med Toxicol 2019 Jan 31;15(1):4-11. Epub 2018 Jul 31.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Introduction: Polydrug use involving heroin and benzodiazepines is common. The potential risk of additive pharmacological effects may be associated with poorer outcomes in patients who use benzodiazepines together with heroin. The aim of this study was to determine the clinical picture of patients presenting to the emergency department following acute drug toxicity involving heroin and benzodiazepines. Read More

Behav Brain Res 2019 02 19;359:871-877. Epub 2018 Jul 19.

Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA. Electronic address:

Alzheimer's disease is marked by the presence of amyloid-beta (Aβ) plaques, elevated central cytokine levels, dysregulation of BDNF-related gene expression, and cognitive decline. Previously, our laboratory has demonstrated that repeated administration of peripheral LPS is sufficient to significantly increase the presence of central Aβ in the hippocampus, and that this upregulation corresponds with deficits in learning and memory. We have also previously demonstrated that the inverse benzodiazepine agonist MRK-016 (MRK) can protect against memory acquisition and consolidation errors in mice. Read More

Am J Case Rep 2018 Jul 16;19:833-835. Epub 2018 Jul 16.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA.

BACKGROUND Serotonin syndrome is a life-threatening condition that can lead to neurologic complications and is associated with the use of serotonergic medications. As the use of antidepressant medications has increased, the incidence of perioperative serotonin syndrome has transitioned from a rare diagnosis to one that should be considered as a differential diagnosis for any patient displaying signs of neuroexcitation. CASE REPORT A 70-year-old man (ASA 2) with a history of vestibular migraines (treated with venlafaxine), gastroesophageal reflux disease, and benign prostatic hyperplasia presented to our institution for photoselective vaporization of the prostate. Read More

Drug Alcohol Depend 2018 09 4;190:112-119. Epub 2018 Jul 4.

National Institute on Drug Abuse, Division of Epidemiology, Services, and Prevention Research, Rockville, MD, USA.

Background: Little is known about risk factors for repeated opioid overdose and fatal opioid overdose in the first year following nonfatal opioid overdose.

Methods: We identified a national retrospective longitudinal cohort of patients aged 18-64 years in the Medicaid program who received a clinical diagnosis of nonfatal opioid overdose. Repeated overdoses and fatal opioid overdoses were measured with the Medicaid record and the National Death Index. Read More

Drug Alcohol Depend 2018 09 13;190:62-71. Epub 2018 Jun 13.

Tennessee Department of Health, Office of Informatics and Analytics, Andrew Johnson Tower, 7th Floor, 710 James Robertson Parkway, Nashville, TN, 37243, United States; Department of Health Policy, Vanderbilt University Medical Center, 2525 West End Ave, Suite 1200, Nashville, TN, 37203, United States.

Background: Opioid overdose deaths have continued to rise in Tennessee (TN) with fentanyl emerging as a major contributor. Current data are needed to identify at-risk populations to guide prevention strategies. We conducted a large statewide observational study among TN adult decedents (2013-2016) to evaluate the association of sociodemographic factors and prescribing patterns with opioid overdose deaths. Read More

J Anal Toxicol 2018 Nov;42(9):655-660

Forensic Science SA (Toxicology), Adelaide, South Australia, Australia.

The number of new psychoactive substances (NPS) available is constantly increasing, making it difficult for toxicology laboratories to keep screening methods up to date. Full scan high-resolution mass spectrometry (HRMS) is a versatile technique which allows for progressive updating of spectral databases to increase the scope of screening. It also allows for retrospective screening of data-specifically, reprocessing of data files using an updated spectral database without the need for re-extraction or reanalysis. Read More

J Forensic Sci 2019 Jan 25;64(1):149-153. Epub 2018 Jun 25.

Michigan Medicine Department of Pathology/Wayne County Medical Examiner's Office, 1300 E Warren Ave, Detroit, MI, 48207.

Acetyl fentanyl (N-[1-phenethylpiperidin-4-yl]-N-phenylacetamide) is a potent opioid analgesic with no medicinal uses. We report deaths between 2016 and 2017 at the Medical Examiner's Office in Detroit, MI where acetyl fentanyl was found in the decedent's blood and compare them to previously published deaths between 2015 and 2016. The recent cases (cohort B) had a mean acetyl fentanyl concentration of 0. Read More

Acute Med 2018 ;17(2):96-97

Haseki Training and Research Hospital, Department of Emergency Medicine, Istanbul, Turkey.

Olanzapine is an antipsychotic drug used in psychiatric diseases. At high doses it exhibits cardiovascular and neurological sideeffects in particular. Lipid emulsion therapy for the removal of medication from plasma in high-dose lipophilic drug use has recently become very widespread. Read More

Expert Opin Drug Metab Toxicol 2018 Jun;14(6):551-559

a Department of Forensic Medicine, School of Basic Medical Sciences , Fudan University , Shanghai , China.

Background: Alprazolam is a commonly used benzodiazepine in clinical practice, and when coingested with ethanol, alprazolam can increase behavioral irritability and aggression. However, the mechanism of its interaction with ethanol remains unknown.

Research Design And Methods: The pharmacokinetics of alprazolam was studied in vivo in rat experiments involving the simultaneous administration of alprazolam and ethanol, and the interactions between ethanol and alprazolam were investigated in vitro in human liver microsomes. Read More

Adv Pharmacol Sci 2018 1;2018:6042602. Epub 2018 Apr 1.

PharmacodynamyResearch Team PRT, Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, Mohammed V University, BP 6203, Rabat, Morocco.

The objective of our work is to make a pharmacological study of molecules derived from 4-phenyl-1,5-benzodiazepin-2-one carrying long chains so that they have a structure similar to surfactants, with the benzodiazepine as a hydrophilic head and a carbon chain as a hydrophobic tail. First, we studied the acute toxicity of the above mentioned 4-phenyl-1,5-benzodiazepin-2-one derivatives. This study was conducted according to OECD 423 guidelines in female mice and revealed that these compounds are nontoxic. Read More

Biochim Biophys Acta Mol Basis Dis 2018 09 23;1864(9 Pt B):2845-2858. Epub 2018 May 23.

Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, College of Medicine, Bryan, TX 77807, USA. Electronic address:

Nerve agents and some pesticides such as diisopropylfluorophosphate (DFP) cause neurotoxic manifestations that include seizures and status epilepticus (SE), which are potentially lethal and carry long-term neurological morbidity. Current antidotes for organophosphate (OP) intoxication include atropine, 2-PAM and diazepam (a benzodiazepine for treating seizures and SE). There is some evidence for partial or complete loss of diazepam anticonvulsant efficacy when given 30 min or later after exposure to an OP; this condition is known as refractory SE. Read More

Med Chem 2019 ;15(1):77-86

Escuela Superior de Medicina, Instituto Politecnico Nacional, Plan de San Luis y Díaz Mirón s/n Col. Casco de Santo Tomas, Del. Miguel Hidalgo, 11340, Mexico City, Mexico.

Background: Benzofurans are heterocyclic compounds with neurotropic activity. Some have been developed for the treatment of acute and degenerative neuronal injuries.

Objective: The study aimed to evaluate the in silico binding of some promising benzofurans on the GABA receptors, and the in vivo neurotropic activity of benzofuran analogues (BZF 6-10) of gamma-aminobutyric acid (GABA) on a seizure model. Read More