Search Our Scientific Publications & Authors

Psychogeriatrics 2022 May 13. Epub 2022 May 13.

Unit for Aging Brain and Dementia, Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.

Background: Widespread prescription of antidepressants and their resulting role in serotonin syndrome (SS) are of great importance for clinical practice in the elderly. This study aims to investigate possible associations of antidepressant drug-induced SS with related variables in these patients.

Methods: A total of 238 older adults using antidepressants were included. Read More

Curr Pharm Des 2022 May 10. Epub 2022 May 10.

Drug Misuse & Novel Psychoactive Substances Research Unit, School of Life & Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield, United Kingdom.

Background: Previous studies have reported that benzodiazepines (BZDs) seem to enhance euphoric and reinforcing properties of opioids in opioid users so that a direct effect on opioid receptors has been postulated together with possible synergistic induction of severe side-effects due to their co-use. This is particularly worrisome given the appearance on the market of designer benzodiazepines (DBZDs), whose activity/toxicity profiles are scarcely known.

Objectives: This study aimed to evaluate, through computational studies, the binding affinity (or lack thereof) of 101 DBZDs identified online on the kappa, mu, and delta opioid receptors (K, M, DOR); and to assess whether their mechanism of action could include activity on t of the latter Methods. Read More

Forensic Sci Int 2022 Apr 30;336:111324. Epub 2022 Apr 30.

Service de Pharmacologie-Toxicologie et Pharmacovigilance, CHU Angers, Angers, France.

During the last decade, only few cases of acute etizolam intoxication have been detailed. Little is known about the toxic effects of etizolam overdose. Here, the authors report the case of a 42-year-old man who was admitted to the emergency department for intense agitation following etizolam and cocaine consumption. Read More

J Forensic Leg Med 2022 May 26;88:102356. Epub 2022 Apr 26.

PO Box 498, Northwich, Cheshire, CW9 9BE, UK.

Oral methadone may be prescribed to detainees with the aim of minimising the risk of fatal opioid poisoning on release. To study the circumstances under which methadone-related deaths can occur in detention, we audited reports of 17 [14 male, 3 female; median (range) age 34 (22-52) years] such deaths, July 2010-December 2011. The median (range) methadone dose was 40 (10-110) mg/d (N = 16). Read More

Ecotoxicol Environ Saf 2022 Jun 28;238:113568. Epub 2022 Apr 28.

College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, People's Republic of China; Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing 100013, People's Republic of China. Electronic address:

Chlorinated disinfection byproducts in water posed potential health threat to humans. Nowadays, chlorinated derivatives of diazepam were ubiquitously detected in drinking water. Among these derivatives, 2-methylamino-5-chlorobenzophenone (MACB) was capable of penetrating the blood-brain barrier (BBB) and induced microglial phagocytosis of neurons in zebrafish. Read More

BMJ Open 2021 Dec 30;11(12):e052057. Epub 2021 Dec 30.

Sealy Center on Aging, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA.

Objective: Examine the association between the co-prescribing of opioids, benzodiazepines, gabapentinoids (pregabalin and gabapentin) and selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors (SSRI/SNRIs) in different combinations and the risk of falls and fractures.

Design: Retrospective cohort study from 2015 to 2018.

Setting: Medicare enrolment and claims data. Read More

Cureus 2022 Mar 19;14(3):e23310. Epub 2022 Mar 19.

Internal Medicine, Icahn School of Medicine at Mount Sinai, Elmhurst Hospital Center, Elmhurst, USA.

As a renowned local anesthetic agent of choice, lidocaine is also a class 1b antiarrhythmic agent that is primarily used for the treatment of ventricular arrhythmias. Although lidocaine systemic toxicity is rare, it may be life-threatening; thus, its early identification and management are of vital importance. This case report details the clinical scenario of intravenous lidocaine administration to a patient at high risk of toxicity in a 64-year-old patient, who initially presented with sustained monomorphic ventricular tachycardia received lidocaine and subsequently developed neurologic manifestations of lidocaine toxicity, including altered mental status and seizure. Read More

Neurotox Res 2022 Jun 22;40(3):751-762. Epub 2022 Apr 22.

Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China.

Central nervous system (CNS) dysfunction induced by sepsis and pathogenic microbial infections is reported to be closely associated with increased permeability of the blood-brain barrier (BBB), which is mainly mediated by the stimulation of lipopolysaccharide (LPS) on inflammatory signaling. Midazolam is a novel sedative acting on the benzodiazepine receptor, which is recently reported to exert a neuroprotective effect by inhibiting inflammation. The present study will explore the potential repair capacity of Midazolam on LPS-induced damage to the BBB. Read More

Am J Emerg Med 2022 Mar 31. Epub 2022 Mar 31.

Department of Critical Care Medicine, Taipei Medical University Hospital, Taipei City, Taiwan; Department of Emergency Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; Graduate Institute of Injury Prevention and Control, College of Public Health, Taipei Medical University, Taipei City, Taiwan. Electronic address:

We report a case of a young male with amphetamine toxicity initially obscured by concomitant use of gamma-hydroxybutyrate (GHB), and the sympathomimetic symptoms emerged after GHB's effects receded. A 24-year-old unconscious man presented to emergency department showed the following vital signs upon admission: blood pressure 136/58 mmHg; heart rate 79 bpm; SpO2 87% under ambient air; body temperature 36.1 °C; Glasgow Coma Scale score 3. Read More

J Pharm Biomed Anal 2022 May 5;214:114751. Epub 2022 Apr 5.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin 124221, PR China; The First Hospital of Jilin University, Jilin University, Xinmin Street, Changchun 130061, PR China. Electronic address:

Therapeutic drug monitoring of carbamazepine is necessary for its clinical application with the purpose to reach therapeutic concentration and reduce the risk of concentration-dependent toxicity. An ultrafast analytical assay for quantification of carbamazepine in human plasma was developed and validated based on direct analysis in real time tandem mass spectrometry (DART-MS/MS). After reversed phase solid phase extraction with Waters Oasis HLB, carbamazepine and internal standard carbamazepine-DN were monitored by positive ion mode followed by multiple reaction monitoring (MRM) of the transitions at m/z 237. Read More

Neurotox Res 2022 Jun 7;40(3):892-899. Epub 2022 Apr 7.

Department of Pharmacology, Howard University College of Medicine, 520 W Street NW, Washington, DC, USA.

Toxicity induced by binge alcohol drinking, particularly in adolescent and young adults, is of major medical and social consequence. Recently, we reported that butyrate, a short chain fatty acid, can protect against ethanol (ETOH)-induced toxicity in an in vitro model. In this study, we sought to evaluate the potential effectiveness of dihydromyricetin (DHM), a natural bioactive flavonoid, alone or in combination with butyrate in the same model. Read More

Drug Alcohol Depend 2022 04 24;233:109376. Epub 2022 Feb 24.

Centre for Pharmaceutical Medicine Research, Institute of Pharmaceutical Medicine, King's College London, Franklin-Wilkins Building, Stamford Street, London SE1 9NH, UK; National Programme on Substance Abuse Deaths, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK.

Background: Dihydrocodeine (DHC) is considered a 'weak' opioid, but there is evidence of its increasing misuse in overdose deaths. This research aims to analyse trends in DHC-related deaths in England relevant to source and dose of DHC, and decedent demographics.

Methods: Cases from England reported to the National Programme on Substance Abuse Deaths (NPSAD) where DHC was identified at post-mortem and/or implicated in death between 2001 and 2020 were extracted for analysis. Read More

Aust Vet J 2022 Mar 3. Epub 2022 Mar 3.

Veterinary Specialist Services, Carrara, Queensland, Australia.

Background: 5-Fluorouracil (5-FU) cream is a common human topical chemotherapy agent with potentially fatal neurotoxic effects on dogs if accidentally ingested. There are seldom reports in veterinary literature describing the successful outcome of intervention after accidental ingestion of 5-FU cream.

Case Summary: A 9-month-old spayed female labradoodle presented 14 h after ingesting an unknown amount of 40 g tube of Efudex cream (5% 5-FU). Read More

Braz J Med Biol Res 2022 28;55:e11771. Epub 2022 Feb 28.

Laboratório de Farmacologia e Toxicologia de Produtos Naturais, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.

Seizures are a disorder caused by structural brain lesions, life-threatening metabolic derangements, or drug toxicity. The present study describes the behavior related to proconvulsant activity induced by thiocolchicoside (TCC) in rats and investigates the electrocorticographic patterns of this behavior and the effectiveness of classic antiepileptic drugs used to control these seizures. Forty-nine adult male Wistar rats were used and divided into two phases of our experimental design: 1) evaluation of seizure-related behavior and electrocorticographic patterns induced by TCC and 2) evaluation of the efficacy of classical antiepileptic drugs to control the proconvulsive activity caused by TCC. Read More

Iran J Pharm Res 2021 ;20(4):47-58

Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Benzodiazepines (BZD) are among the main classes of tranquilizing drugs, bearing much less toxicity compared to other drugs acting on the CNS. Considering the pharmacophore model of BZD binding to GABA-A receptor, novel diphenyl 1,3,4-oxadiazole compounds as BZD ligands were designed. The compounds were synthesized and structurally confirmed using LCMS, IR and NMR techniques. Read More

Subst Abuse Rehabil 2022 9;13:13-23. Epub 2022 Feb 9.

Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.

Recreational gamma-hydroxybutyrate (GHB) use, although less common than other substance use, is increasingly recognised and is over-represented in emergency toxicology presentations. This narrative review summarizes GHB pharmacology, current patterns of use, potential harms and management of GHB toxicity and withdrawal. There is a complex interplay between GHB and GABA as GHB is both a prodrug and metabolite of GABA and GHB activates both GHB and GABA receptors. Read More

J Addict Med 2022 Feb 4. Epub 2022 Feb 4.

Grayken Center for Addiction, Boston Medical Center, Boston, MA, USA (AFP, MTHH); Section of General Internal Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA (AFP, MTHH); Clinical Addiction Research and Education (CARE) Unit, Boston Medical Center, Boston, MA, USA (AFP, MTHH); Department of Psychiatry, Boston Medical Center, Boston, MA, USA (RA); Department of Family Medicine, Boston Medical Center, Boston, MA, USA (RA).

Background: Phenibut is a non-Food and Drug Administration-approved gamma-aminobutyric acid analog marketed in the United States as an anxiolytic, cognitive enhancer, and alcohol withdrawal treatment through online supplement vendors. In this case report, we describe a woman's self-directed detoxification with phenibut used to manage withdrawal symptoms from fentanyl and benzodiazepines in March 2020 during the height of the COVID-19 pandemic.

Case: A 38-year-old woman with severe opioid, benzodiazepine, gabapentin, stimulant use disorders developed altered mental status after oral phenibut ingestion intended to help self-manage opioid and benzodiazepine withdrawal. Read More

Cardiovasc Toxicol 2022 May 1;22(5):419-435. Epub 2022 Feb 1.

Reproductive Physiology and Bioinformatics Research Unit, Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.

The global prevalence of illicit drug use is on the increase with attendant complications like cardiorenal collapse. One such substance of abuse is rohypnol. Despite its ban in most countries, it remains a popular substance of abuse. Read More

J Natl Cancer Inst 2022 May;114(5):753-760

Office of Research and Development, Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.

Background: There is limited research on how the opioid epidemic and consequent risk reduction policies have affected pain management among cancer patients. The purpose of this study was to analyze how the Opioid Safety Initiative (OSI) implemented at the Veterans Health Administration affected opioid prescribing patterns and opioid-related toxicity.

Methods: We performed an interrupted time series analysis of 42 064 opioid-naïve patients treated at the Veterans Health Administration for prostate, lung, breast, and colorectal cancer from 2011 to 2016. Read More

Eur J Med Chem 2022 Feb 11;230:114060. Epub 2022 Jan 11.

Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664, Warsaw, Poland. Electronic address:

Tetrazole and benzodiazepine derivatives attract widespread attention due to their remarkable pharmaceutical potential. 5-(2-bromophenyl)-7-fluoro-1-[3-(5-(4-chlorophenyl)-2H-tetrazol-2-yl)propyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one (6c) and 5-(2-bromophenyl)-7-fluoro-1-[3-(5-(2-chlorophenyl)-2H-tetrazol-2-yl)propyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one (6d) were selected using the microdilution approach and because of their preferential fungicidal activity toward C. albicans. Read More

J Emerg Med 2022 03 20;62(3):332-336. Epub 2022 Jan 20.

Division of Medical Toxicology, Department of Emergency Medicine, University of California-San Diego, San Diego, California.

Background: Hydroxychloroquine overdose is rare but potentially lethal. Hydroxychloroquine overdose symptoms are characterized by central nervous system toxicity, cardiac toxicity, and hypokalemia. Recommended treatment consists of epinephrine, high-dose diazepam, and careful potassium repletion. Read More

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

Neurosci Lett 2022 02 15;771:136459. Epub 2022 Jan 15.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Taiping Road 27, Beijing 100850, China. Electronic address:

Opioid analgesics are widely used to treat acute, postoperative, and chronic pain. However, opioid receptor activation can result in severe respiratory depression. In this study, we demonstrated that Tandospirone (TS), a selective serotonin-1A receptor partial agonist, is effective against opioid-induced respiratory depression. Read More

Drug Alcohol Depend 2022 03 10;232:109292. Epub 2022 Jan 10.

National Drug & Alcohol Research Centre, University of New South Wales, NSW, Australia; School of Psychiatry, University of New South Wales, NSW, Australia.

Background: Aims: To determine 1. The characteristics of all recorded cases of fatal drug poisoning involving novel synthetic opioids (NSOs) in Australia; 2. The toxicology of cases; and 3. Read More

Drug Alcohol Depend 2022 02 31;231:109244. Epub 2021 Dec 31.

Dutch Poisons Information Center (DPIC), University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address:

Background: Designer benzodiazepines (DBs) are an emerging class of new psychoactive substances. While structurally derived from pharmaceutical benzodiazepines, their toxicological profile is less clear. We investigated time trends in the rate of DB poisonings and their clinical toxicity. Read More

Anticancer Drugs 2022 03;33(3):300-307

Institute of Pharmacology, Medical University of Vienna, Vienna.

Small cell lung cancer (SCLC) is frequently found disseminated at first presentation and holds a poor prognosis due to emerging resistance to first-line platinum-based and second-line topotecan chemotherapy. The present investigation tested the antitumor activity of rovalpituzumab tesirine (ROVA-T), a cytotoxic anti-DLL3 drug conjugate, against two SCLC and a corresponding SCLC CTC cell line established from a ROVA-T-resistant patient to characterize the mechanism of recurrence. Two cell lines were established from an SCLC patient progressing under ROVA-T therapy and characterized with respect to chemosensitivity against this drug as well as against currently applied chemotherapeutics and for their delta-like 3 (DLL3) expression. Read More

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Nov;46(11):1203-1211

School of Public Health, Shaanxi University of Chinese Medicine, Xianyang Shaanxi 712046, China.

Objectives: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 can damage the myocardium directly, or activate the immune system, trigger a cytokine storm, and cause inflammatory cells to infiltrate the myocardial tissue and damage the myocardium. This study is based on the sequencing data to analyze the changes in gene expression of cardiomyocytes and macrophages after SARS-CoV-2 infection, and explore the potential effects of SARS-CoV-2 on the heart and immune system. Read More

Forensic Sci Int 2022 Feb 5;331:111140. Epub 2021 Dec 5.

National Drug & Alcohol Research Centre, University of New South Wales, NSW, Australia; School of Psychiatry, University of New South Wales, NSW, Australia.

Introduction: The study aimed to determine: 1. The characteristics of all recorded cases of fatal drug poisoning involving 'novel' benzodiazepines (NBZDs) in Australia; 2. The toxicology of cases; and 3. Read More

Br J Anaesth 2022 03 4;128(3):584-595. Epub 2021 Dec 4.

Université Paris-Saclay - CEA - CNRS - Inserm - BioMaps, Orsay, France.

Background: The safety profile of buprenorphine has encouraged its widespread use. However, fatalities have been attributed to benzodiazepine/buprenorphine combinations, by poorly understood mechanisms of toxicity. Mechanistic hypotheses include (i) benzodiazepine-mediated increase in brain buprenorphine (pharmacokinetic hypothesis); (ii) benzodiazepine-mediated potentiation of buprenorphine interaction with opioid receptors (receptor hypothesis); and (iii) combined effects of buprenorphine and benzodiazepine on respiratory parameters (pharmacodynamic hypothesis). Read More

Transpl Immunol 2022 04 29;71:101510. Epub 2021 Nov 29.

Anesthesiology Department, The Forth people's hospital of Jinan, China.

Background: Lidocaine was an anesthetic commonly used for analgesia, but the neurotoxicity could not be ignored. However, benzodiazepines could alleviate the toxicity when combined with other drugs.

Purpose: To explore the molecular mechanism of benzodiazepines in protecting nerve cells after the induction of lidocaine. Read More