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J Biomol Struct Dyn 2022 Mar 23:1-13. Epub 2022 Mar 23.

Department of Chemistry, K.N.Toosi University of Technology, Tehran, Iran.

Dihydrofolate reductase (DHFR) is a ubiquitous cellular enzyme involved in the biosynthesis of nucleotide and protein precursors, thus, the inhibition of human DHFR can be a promising strategy in cancer treatment. The design of effective anticancer drugs is an urgent need today according to the high spread of cancer. The indole molecule with diverse mechanisms of action and anticancer properties is one of the efficient pharmacophores in drug design. 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

Mol Divers 2022 Jan 19. Epub 2022 Jan 19.

Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran.

Cancer as one of the biggest human health problems remains unsolved. The identification of novel platforms with the highest efficacy and low toxicity is a big challenge among interested researchers. In this regard, we are interested to synthesis and evaluate antitumor activity of spiro[indolo[2,1-b]quinazoline-pyrano[2,3-d]pyrimidine] and spiro[indolo[2,1-b]quinazoline-pyrido[2,3-d]pyrimidine] derivatives. Read More

Toxicol In Vitro 2022 Apr 14;80:105311. Epub 2022 Jan 14.

ScitoVation, 6 Davis Drive, Suite 146, Durham, NC 27709, United States of America.

There is increasing interest in using modern 'omics technologies, such as whole transcriptome sequencing, to inform decisions about human health safety and chemical toxicity hazard. High throughput methodologies using in vitro assays offer a path forward in reducing or eliminating animal testing. However, many aspects of these technologies need assessment before they will gain the trust of regulators and the public as viable alternative test methods for human health and safety. Read More

Front Nutr 2021 14;8:788929. Epub 2021 Dec 14.

College of Bioscience and Bioengineering, Qinba State Key Laboratory of Biological Resources and Ecological Environment, QinLing-Bashan Mountains Bioresources Comprehensive Development C. I. C, Shaanxi Province Key Laboratory of Bio-Resources, Shaanxi University of Technology, Hanzhong, China.

Gastric cancer is one of the most common cancer and deadly disease worldwide. Despite substantial advances made in the treatment of gastric cancer, existing therapies still encounter bottlenecks. Chemotherapy, for instance, could lead to serious side effects, high drug resistance and treatment failure. Read More

Adv Clin Exp Med 2022 Mar;31(3):285-292

Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Turkey.

Background: In the literature, it has been suggested that ketamine-related oxidative organ damage results from increased blood adrenaline level, and thiopental-related oxidative damage is caused by decreased adrenaline level, suggesting that ketamine-thiopental combination (KT) may be beneficial in reducing the hepatotoxic effect of ketamine.

Objectives: To biochemically investigate the effects of ketamine, thiopental and KT on the liver in rats.

Material And Methods: Male albino Wistar type rats received intraperitoneally (ip. Read More

Toxicology 2021 12 4;464:153023. Epub 2021 Nov 4.

Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany. Electronic address:

Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) represent a sub-group of persistent organic pollutants found in food, environmental samples and human and animal tissues. Promotion of pre-neoplastic lesions in rodent liver has been suggested as an indicator for a possible increased risk of liver cancer in humans exposed to NDL-PCBs. In rodent hepatocytes, suppression of DNA damage-triggered apoptosis is a typical mode of action of liver tumor promoters. Read More

Biomedicines 2021 Oct 11;9(10). Epub 2021 Oct 11.

CICS-UBI-Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.

Xanthine oxidase (XO) is the enzyme responsible for the conversion of endogenous purines into uric acid. Therefore, this enzyme has been associated with pathological conditions caused by hyperuricemia, such as the disease commonly known as gout. Barbiturates and their congeners thiobarbiturates represent a class of heterocyclic drugs capable of influencing neurotransmission. Read More

Epilepsia Open 2021 12 23;6(4):757-769. Epub 2021 Oct 23.

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

Objective: Cholinergic-induced status epilepticus (SE) is associated with a loss of synaptic gamma-aminobutyric acid A receptors (GABA R) and an increase in N-methyl-D-aspartate receptors (NMDAR) and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) that may contribute to pharmacoresistance when treatment with benzodiazepine antiseizure medication is delayed. The barbiturate phenobarbital enhances inhibitory neurotransmission by binding to a specific site in the GABA R to increase the open state of the channel, decrease neuronal excitability, and reduce glutamate-induced currents through AMPA/kainate receptors. We hypothesized that phenobarbital as an adjunct to midazolam would augment the amelioration of soman-induced SE and associated neuropathological changes and that further protection would be provided by the addition of an NMDAR antagonist. Read More

J Pharmacol Toxicol Methods 2021 Nov-Dec;112:107107. Epub 2021 Aug 5.

Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.

Administration of a compound can induce drug-metabolizing enzymes (DMEs) in the liver. DME induction can affect various parameters in toxicology studies. Therefore, evaluation of DME induction is important for interpreting test compound-induced biological responses. Read More

Food Chem Toxicol 2021 Oct 18;156 Suppl 1:112425. Epub 2021 Jul 18.

Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ, 07677, USA. Electronic address:

Crit Rev Toxicol 2021 05 15;51(5):373-394. Epub 2021 Jul 15.

Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.

Many nongenotoxic chemicals have been shown to produce liver tumors in mice and/or rats by a mode of action (MOA) involving activation of the constitutive androstane receptor (CAR). Studies with phenobarbital (PB) and other compounds have identified the key events for this MOA: CAR activation; increased hepatocellular proliferation; altered foci formation; and ultimately the development of adenomas/carcinomas. In terms of human relevance, the pivotal species difference is that CAR activators are mitogenic agents in mouse and rat hepatocytes, but they do not stimulate increased hepatocellular proliferation in humans. Read More

Transfus Apher Sci 2021 Oct 18;60(5):103173. Epub 2021 Jun 18.

Department of Pediatrics, Ankara City Hospital, Ankara, Turkey.

Except for side effects expected standart dose use of the chemotherapeutics agents, toxic effects (poisoning) may occur if high doses of are mistakenly used in the treatment of haemato-oncological diseases and these toxic doses are usually fatal. Here, we report a case of Stevens Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) following administration of toxic dose of vinblastine by mistake. A 20-month-old male patient with a diagnosis of Langerhans Cell Histiocytosis (Letterer-Siwe) at the pediatric oncology department was admitted to intensive care unit, after having received treatment protocol consisting of vinblastine, etoposide and prednisolone, with fever, altered consciousness and decompensated shock findings. Read More

Chemistry 2021 Sep 29;27(50):12877-12883. Epub 2021 Jul 29.

Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, ITI Chimie des Systèmes Complexes, Université de Strasbourg, 74 route du Rhin, 67401, Illkirch, France.

Bulky hydrophobic counterions (weakly coordinating anions) can insulate ionic dyes against aggregation-caused quenching (ACQ) and enable preparation of highly fluorescent dye-loaded nanoparticles (NPs) for bioimaging, biosensing and light harvesting. Here, we introduce a family of hydrophobic anions based on fluorinated C-acyl barbiturates with delocalized negative charge and bulky non-polar groups. Similarly to fluorinated tetraphenylborates, these barbiturates prevent ACQ of cationic dye alkyl rhodamine B inside polymer NPs made of biodegradable poly(lactic-co-glycolic acid) (PLGA). Read More

Leg Med (Tokyo) 2021 Nov 7;53:101928. Epub 2021 Jun 7.

Forensic Science South Australia (FSSA) and the Adelaide Medical School, The University of Adelaide, Adelaide, South Australia 5000, Australia. Electronic address:

A study was undertaken of 51 cases where barbiturates were detected in post-mortem blood samples from 2000 to 2019 at Forensic Science South Australia, Adelaide, Australia. The cause of death was drug toxicity in only 27 (53%) (M:F = 19:8; age range 19-74yrs, mean 46yrs). In 17 cases, barbiturate toxicity was the primary cause of death, 14 due to pentobarbitone and 3 to phenobarbitone. Read More

Drug Metab Pers Ther 2020 Dec 29. Epub 2020 Dec 29.

Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Lagos State, Nigeria.

Objectives: Concurrent use of herbs with drugs have become a major healthcare problem. Herb-drug interactions could lead to therapeutic failure or toxicity. Hence, this study seeks to evaluate the impact of combining rhizome (CL) with selected anxiolytic and hypnotic drugs. Read More

Clin Toxicol (Phila) 2021 06 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

Vet Clin Pathol 2021 Mar 22;50(1):122-131. Epub 2021 Mar 22.

Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.

Background: Cytopenias have been reported in dogs treated with phenobarbital, but detailed descriptions of bone marrow findings and response to treatment are lacking.

Objectives: We aimed to characterize the hematologic findings and clinical outcomes of dogs that had been receiving phenobarbital at the time of marrow evaluation.

Methods: Archived bone marrow slides and clinicopathologic data were reviewed in dogs undergoing marrow evaluation for any hematologic problems that developed while receiving phenobarbital (2008-2020). Read More

Basic Clin Pharmacol Toxicol 2021 Jul 28;129(1):52-60. Epub 2021 Mar 28.

National Engineering Research Center of South China Sea Marine Biotechnology, Guangzhou, China.

Conotoxins, which target ion channels or neurotransmitter receptors with high specificity, are valuable in drug development for pain, epilepsy and other neurological diseases. However, the toxicology of conotoxins is rarely reported. In this study, we primarily researched parts of the pharmacological and toxicological properties of an analgesic conotoxin lt14a. Read More

Mini Rev Med Chem 2021 ;21(17):2481-2496

Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Science and Research, Pimpri, Pune, Maharashtra, India - 411 018 (Affiliated to SPPU, Pune), India.

Background: Hyperlipidemia is characterized by high level of cholesterol and triglycerides in blood. Various classes of drugs like statins, fibrates, niacin etc. are used for treatment of hyperlipidaemia. Read More

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

Neuropharmacology 2021 03 12;185:108449. Epub 2021 Jan 12.

Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.

The sodium-potassium-chloride (Na-K-Cl) cotransporter NKCC1 is found in the plasma membrane of a wide variety of cell types, including neurons, glia and endothelial cells in the brain. Increased expression of neuronal NKCC1 has been implicated in several brain disorders, including neonatal seizures and epilepsy. The loop diuretic and NKCC inhibitor bumetanide has been evaluated as an antiseizure agent alone or together with approved antiseizure drugs such as phenobarbital (PB) in pre-clinical and clinical studies with varying results. 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

CNS Neurol Disord Drug Targets 2021 ;20(2):174-180

Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran.

Objectives: While phenobarbital (PB) is commonly used for the management of seizures in newborns and pediatrics, its administration may accompany acute poisoning. We aimed to review the literature to find out the frequency of PB poisonings in newborns and children with seizures.

Method: A literature search was performed by two independent reviewers to find relevant articles about PB toxicity in neonates and pediatrics that were treated for the seizure. Read More

J Trauma Acute Care Surg 2021 02;90(2):319-324

From the Division of Trauma, Emergency Surgery, and Surgical Critical Care (M.E.M., K.B., G.V., H.M.A.K.), Massachusetts General Hospital; Department of Surgery (J.P.H.-E., A.S.), Division of Trauma, Burn and Surgical Critical Care, Brigham and Women's Hospital, Harvard Medical School; Center for Surgery and Public Health (J.P.H.-E., C.O., A.N.H., A.S.), Brigham and Women's Hospital, Harvard Medical School, Harvard T.H. Chan School of Public Health; Department of Psychiatry (N.C.L.-C.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Trauma, Burn and Critical Care Surgery (D.N.), Harborview Medical Center, University of Washington, Seattle, Washington; Division of Trauma, Acute Care Surgery and Surgical Critical Care (S.E.S.), Boston University School of Medicine, Boston, Massachusetts.

Introduction: Psychoactive drug use (PDU) is reported in up to 40% of trauma patients and is associated with a higher rate of in-hospital complications. However, little is known about its long-term impact on trauma patients. We aimed to assess the long-term functional, mental, and psychosocial outcomes of PDU in trauma patients 6 to 12 months after injury. Read More

Neurochem Res 2021 Feb 18;46(2):396-410. Epub 2020 Nov 18.

Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, PL 20-090, Lublin, Poland.

Protective (antiseizure) effects of 4-butyl-5-[(4-chloro-2-methylphenoxy)-methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) and acute neurotoxic effects were determined in the tonic-clonic seizure model and rotarod test in mice. The interaction profile of four classic antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) with TPL-16 was also determined in the tonic-clonic seizure model in mice. The protective effects of TPL-16 from tonic-clonic seizures (as ED values) and acute neurotoxic effects of TPL-16 (as TD values) were determined in 4 pretreatment times (15, 30, 60 and 120 min after its i. Read More

J Proteome Res 2021 01 26;20(1):950-959. Epub 2020 Oct 26.

Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Luzhou 646000, Sichuan, China.

Drug addiction is a chronic relapsing brain disease. Alterations of glucose uptake and metabolism are found in the brain of drug addicts. Insulin mediates brain glucose metabolism and its abnormality could induce brain injury and cognitive impairment. Read More

Acute Med Surg 2020 Jan-Dec;7(1):e566. Epub 2020 Oct 15.

Yonemori Hospital Kagoshima Japan.

Aim: In 1999, the Japanese Society for Clinical Toxicology proposed 15 toxicants that would be useful for analysis: methanol, barbiturates, benzodiazepines, bromovalerylurea, tricyclic acid, acetaminophen, salicylic acid, theophylline, organic phosphorus pesticides, carbamate pesticides, glufosinate, paraquat, arsenic, cyanide, and methamphetamine. We aimed to reveal the current state of drug analysis for acute poisoning in the emergency department of Japanese hospitals.

Methods: From 1 April, 2017, we undertook a questionnaire survey in the emergency departments of 546 hospitals designated as educational institutions for emergency physicians. Read More

Neurocrit Care 2021 06 30;34(3):1072-1089. Epub 2020 Sep 30.

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

The aim of this narrative review is to describe the toxicologic confounders of brain death currently reported in the literature to offer guidance for physicians assessing brain death after a toxic exposure. We established an a priori definition of a "brain death mimic" as an unresponsive, intubated patient missing some, but not all brainstem reflexes. We completed a review of the literature utilizing MEDLINE and EMBASE to find case reports of patients of all ages in English, French, and Spanish meeting the criteria and hand searched the references of the results. Read More