Oral Fluid to Blood Concentration Ratios of Different Psychoactive Drugs in Samples from Suspected Drugged Drivers
Conclusions: High OF/B ratios were found for amphetamines and opioids, reflecting a high degree of drug transfer from blood to oral fluid and a longer detection window in oral fluid than in blood. For benzodiazepines, low OF/B ratios were found. Results of the concentration measurements in oral fluid from both sides of the mouth could indicate that some remnants of THC and buprenorphine were present in the oral cavity. The large variations among individuals and between the 2 sides of the mouth suggest that drug concentrations in oral fluid do not accurately reflect drug concentrations in the blood. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research

Preclinical characterization of zuranolone (SAGE-217), a selective neuroactive steroid GABAA receptor positive allosteric modulator.
Abstract Zuranolone (SAGE-217) is a novel, synthetic, clinical stage neuroactive steroid GABAA receptor positive allosteric modulator designed with the pharmacokinetic properties to support oral daily dosing. In vitro, zuranolone enhanced GABAA receptor current at nine unique human recombinant receptor subtypes, including representative receptors for both synaptic (γ subunit-containing) and extrasynaptic (δ subunit-containing) configurations. At a representative synaptic subunit configuration, α1β2γ2, zuranolone potentiated GABA currents synergistically with the benzodiazepine diazepam...
Source: Neuropharmacology - September 22, 2020 Category: Drugs & Pharmacology Authors: Althaus AL, Ackley MA, Belfort GM, Gee SM, Dai J, Nguyen DP, Kazdoba TM, Modgil A, Davies PA, Moss SJ, Salituro FG, Hoffmann E, Hammond RS, Robichaud AJ, Quirk MC, Doherty JJ Tags: Neuropharmacology Source Type: research

Inhibitory Effect of Imperatorin on the Pharmacokinetics of Diazepam In Vitro and In Vivo
BackgroundDiazepam is a benzodiazepine drug used to treat anxiety, insomnia, and muscle spasms. Imperatorin is a phytochemical isolated from medicinal plants and is widely used in herbal medicine. The aim of this study was to investigate the interactions between imperatorin and diazepam in vitro and in vivo and to provide evidence-based guidance for the safe clinical use of the drug.MethodsIn vitro inhibition of imperatorin was assessed by incubating rat liver microsomes with diazepam to determine IC50 values and the type of inhibition. For in vivo assessment, six rats were pretreated with 50 mg/kg imperatorin for two week...
Source: Frontiers in Pharmacology - September 16, 2020 Category: Drugs & Pharmacology Source Type: research

Hydroxychloroquine Overdose: What Are the Exact Roles of Diazepam and Potassium Infusion?
chi A PMID: 32926302 [PubMed - as supplied by publisher] (Source: Journal of Medical Toxicology)
Source: Journal of Medical Toxicology - September 14, 2020 Category: Toxicology Authors: Mégarbane B, Schicchi A Tags: J Med Toxicol Source Type: research

In Reply to "Hydroxychloroquine Overdose: What Are the Exact Roles of Diazepam and Potassium Infusion?"
In Reply to "Hydroxychloroquine Overdose: What Are the Exact Roles of Diazepam and Potassium Infusion?" J Med Toxicol. 2020 Sep 14;: Authors: Chai PR, Ferro EG, Kirshenbaum JM, Hayes BD, Culbreth SE, Boyer EW, Erickson TB PMID: 32926301 [PubMed - as supplied by publisher] (Source: Journal of Medical Toxicology)
Source: Journal of Medical Toxicology - September 14, 2020 Category: Toxicology Authors: Chai PR, Ferro EG, Kirshenbaum JM, Hayes BD, Culbreth SE, Boyer EW, Erickson TB Tags: J Med Toxicol Source Type: research

Diazepam and SL-327 synergistically attenuate anxiety-like behaviours in mice - Possible hippocampal MAPKs specificity.
Abstract Intracellular signalling pathways have been extensively studied as therapeutic targets for the treatment of mental diseases. Our attention has been caught by two kinases potentially involved in anxiety, ERK1/2 and CaMKII. The study aimed to examine changes in the activation of ERK1/2 and CaMKII concerning anxiolytic-like behaviours in mice. To evaluate anxiety-related response in mice, we used the open field test and the elevated plus maze test. Behavioural studies were complemented with the immunoblotting analysis to identify proteins of interest in the cortex, hippocampus, and striatum. We analysed the ...
Source: Neuropharmacology - September 12, 2020 Category: Drugs & Pharmacology Authors: Michalak A, Wnorowski A, Berardinelli A, Zinato S, Rusinek J, Budzyńska B Tags: Neuropharmacology Source Type: research

Acetylcholinesterase inhibitors (nerve agents) as weapons of mass destruction: History, mechanisms of action, and medical countermeasures.
Abstract Nerve agents are organophosphorus acetylcholinesterase inhibitors. Acute exposure to nerve agents can cause rapid death. In this review, we summarize the history of nerve agent development and use in warfare, the mechanisms by which these agents cause death or long-term brain damage, and the treatments for preventing death or long-term morbidity. The G-series nerve agents, tabun, sarin, soman, ethyl sarin, and cyclosarin, were developed by the Nazis. VX, the best-known of the V-series agents, was synthesized in the 1950's by a British scientist. Little is known about the development of the novichoks (the ...
Source: Neuropharmacology - September 5, 2020 Category: Drugs & Pharmacology Authors: Aroniadou-Anderjaska V, Apland JP, Figueiredo TH, De Araujo Furtado M, Braga MF Tags: Neuropharmacology Source Type: research

Acute administration of diazepam or midazolam minimally alters long-term neuropathological effects in the rat brain following acute intoxication with diisopropylfluorophosphate.
in PJ Abstract Acute intoxication with organophosphorus cholinesterase inhibitors (OPs) can trigger seizures that rapidly progress to life-threatening status epilepticus. Diazepam, long considered the standard of care for treating OP-induced seizures, is being replaced by midazolam. Whether midazolam is more effective than diazepam in mitigating the persistent effects of acute OP intoxication has not been rigorously evaluated. We compared the efficacy of diazepam vs. midazolam in preventing persistent neuropathology in adult male Sprague-Dawley rats acutely intoxicated with the OP diisopropylfluorophosphate (DFP)....
Source: European Journal of Pharmacology - September 5, 2020 Category: Drugs & Pharmacology Authors: Supasai S, González EA, Rowland DJ, Hobson B, Bruun DA, Guignet MA, Soares S, Singh V, Wulff H, Saito N, Harvey DJ, Lein PJ Tags: Eur J Pharmacol Source Type: research

Assessing the Risk/Benefit at Status Epilepticus Onset: The Prognostic Scores
This study describes and compares the three available scores (Status Epilepticus Severity Score, Epidemiology-Based Mortality Score in Status Epilepticus and Encephalitis, Nonconvulsive, Diazepam resistance, Imaging, Tracheal intubation). (Source: Journal of Clinical Neurophysiology)
Source: Journal of Clinical Neurophysiology - September 1, 2020 Category: Neurology Tags: Invited Review Source Type: research

Axonal mechanisms mediating γ-aminobutyric acid receptor type A (GABA-A) inhibition of striatal dopamine release
Axons of dopaminergic neurons innervate the striatum where they contribute to movement and reinforcement learning. Past work has shown that striatal GABA tonically inhibits dopamine release, but whether GABA-A receptors directly modulate transmission or act indirectly through circuit elements is unresolved. Here, we use whole-cell and perforated-patch recordings to test for GABA-A receptors on the main dopaminergic neuron axons and branching processes within the striatum of adult mice. Application of GABA depolarized axons, but also decreased the amplitude of axonal spikes, limited propagation and reduced striatal dopamine...
Source: eLife - September 1, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication
The rapid antidepressant effect of ketamine has become a breakthrough in the research and treatment of depression. Although predictive and modulating factors of the response to ketamine are broadly studied, little is known about optimal concurrent medication protocols. Concerning gamma-aminobutyric acid neurotransmission being a shared target for both ketamine and benzodiazepines (BZD), we evaluated the influence of BZD on the antidepressant effect of a single ketamine infusion in depressed patients. Data from 47 patients (27 females) with major depression (MADRS ≥ 20, ≥ 1 prior nonresponse to antidepressant treatmen...
Source: Frontiers in Psychiatry - August 28, 2020 Category: Psychiatry Source Type: research

Intramuscular Midazolam for treatment of Status Epilepticus.
Authors: Riva A, Iapadre G, Grasso EA, Balagura G, Striano P, Verrotti A Abstract INTRODUCTION: Status epilepticus (SE) is a common neurological and medical emergency. It has high mortality and morbidity rates, which typically correlate with seizure semiology and duration; therefore, prompt and proper pharmacological intervention is paramount. In a pre-hospital setting, establishing venous access can be difficult, so other routes of drug administration should be considered. AREAS COVERED: The paper summarizes the data from the literature and provides an evaluation of the efficacy and safety of intramuscular mid...
Source: Expert Opinion on Pharmacotherapy - August 27, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research

Dispensing patterns of medicines prescribed by Australian dentists from 2006 to 2018 – a pharmacoepidemiological study
ConclusionThis study highlights the increasing dispensing pattern and trends of dentist ‐prescribed antibiotics, opioids and benzodiazepines. Further investigation may be required to determine whether the medicine use is appropriate. In the future, this could provide new educational opportunities on the appropriate use of medicines for dentists. (Source: International Dental Journal)
Source: International Dental Journal - August 27, 2020 Category: Dentistry Authors: Joon Soo Park, Amy T. Page, Estie Kruger, Marc Tennant Tags: SCIENTIFIC RESEARCH REPORT Source Type: research

Slow Accumulation and Elimination of Diazepam and Its Active Metabolite With Extended Treatment in the Elderly.
Abstract Age-related changes in disposition of diazepam and its principal active metabolite, desmethyldiazepam (DMDZ), during and after extended dosage with diazepam were studied in healthy volunteers. Eight elderly subjects (ages 61-78 years) and 7 young subjects (21-33 years) received 2.5 mg of diazepam twice daily for 15 days. Predose (trough) concentrations of diazepam and DMDZ were measured during the 15 days of dosing, and in the postdosage washout period. Kinetic properties were determined by nonlinear regression using a sequential drug-to-metabolite pharmacokinetic model. Steady-state plasma concentrations...
Source: The Journal of Clinical Pharmacology - August 27, 2020 Category: Drugs & Pharmacology Authors: Greenblatt DJ, Harmatz JS, Zhang Q, Chen Y, Shader RI Tags: J Clin Pharmacol Source Type: research

Update on Anticonvulsant Therapy in the Emergent Small Animal Patient
Seizures are common in veterinary patients and control is critical to the overall patient health. The benzodiazepine class of drugs (diazepam, midazolam, and lorazepam) often are the drug class of choice; however, levetiracetam and propofol also have been gaining favor as anticonvulsant drugs for acute seizure management. After cessation of seizures, practitioners then can discuss long-term seizure control on a case-by-case basis with clients. (Source: Veterinary Clinics of North America: Small Animal Practice)
Source: Veterinary Clinics of North America: Small Animal Practice - August 25, 2020 Category: Veterinary Research Authors: Heidi L. Barnes Heller Source Type: research

[Assessment and Treatment of Alcohol Withdrawal Syndrome].
Abstract Alcohol withdrawal syndrome (AWS) is the most common and well-known condition occurring after intentional or unintentional cessation or decreasing heavy drinking. Approximately 5-10% of these people are suffering from serious medical and psychiatric problems, withdrawal seizures, perceptual disturbances, and delirium tremens. Despite acute medical conditions with the high mortality of severe AWS, proper management could decrease the severity and mortality of AWS. The Clinical Institute withdrawal assessment for alcohol-revised version is a valid, reliable, and sensitive instrument for assessing the clinic...
Source: Korean J Gastroenter... - August 25, 2020 Category: Gastroenterology Authors: Choi HY, Seo JS, Lee SK Tags: Korean J Gastroenterol Source Type: research

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee.
Abstract PURPOSE: Established tonic-clonic status epilepticus (SE) does not stop in one-third of patients when treated with an intravenous (IV) benzodiazepine bolus followed by a loading dose of a second antiseizure medication (ASM). These patients have refractory status epilepticus (RSE) and a high risk of morbidity and death. For patients with convulsive refractory status epilepticus (CRSE), we sought to determine the strength of evidence for 8 parenteral ASMs used as third-line treatment in stopping clinical CRSE. METHODS: A structured literature search (MEDLINE, Embase, CENTRAL, CINAHL) was performed to i...
Source: Epilepsy Curr - August 21, 2020 Category: Neurology Authors: Vossler DG, Bainbridge JL, Boggs JG, Novotny EJ, Loddenkemper T, Faught E, Amengual-Gual M, Fischer SN, Gloss DS, Olson DM, Towne AR, Naritoku D, Welty TE Tags: Epilepsy Curr Source Type: research

Nose-to-Brain Delivery of Diazepam from an Intranasal Aqua-Triggered In-Situ (ATIS) Gelling Microemulsion: Monitoring Brain Uptake by Microdialysis
The objective of the study was to develop ATIS diazepam (ATIS-diazepam) as an alternative to the injection for epileptic emergencies and evaluate its brain uptake and nose-to-brain targeting efficiency in rats.MethodsATIS-diazepam (1  mg/100 µL) was prepared and characterized for in vitro formulation characteristics. An LC–MS/MS method was developed and validated for the bioanalysis of diazepam. In vivo studies for pharmacokinetics, brain uptake and nasal irritation of intranasal ATIS-diazepam were conducted in rats. Brain u ptake was investigated with brain microdialysis, a highly sensitive technique enab...
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 19, 2020 Category: Drugs & Pharmacology Source Type: research

[ASAP] Imidazodiazepine Anticonvulsant, KRM-II-81, Produces Novel, Non-diazepam-like Antiseizure Effects
ACS Chemical NeuroscienceDOI: 10.1021/acschemneuro.0c00295 (Source: ACS Chemical Neuroscience)
Source: ACS Chemical Neuroscience - August 18, 2020 Category: Neuroscience Authors: Daniel E. Knutson* †, Jodi L. Smith‡, Xingjie Ping§, Xiaoming Jin§, Lalit K. Golani†, Guanguan Li†, V. V. N. Phani Babu Tiruveedhula†, Farjana Rashid†, Md Yeunus Mian†, Rajwana Jahan†, Dishary Sharmin†, Rok Cerne‡∥, James M. Cook Source Type: research

Aqueous Root Bark Extract of Daniellia oliveri (Hutch. & Dalz.) (Fabaceae) Protects Neurons against Diazepam-Induced Amnesia in Mice.
This study was carried out to evaluate the potential neuroprotection effect of the aqueous root bark extract of Daniellia oliveri against diazepam-induced amnesia in mice. Thirty-six adult male mice were distributed into six groups: the three test groups received Daniellia oliveri root bark extract (100, 200, and 300 mg/kg), the normal control group received distilled water (10 ml/kg), a positive control group received piracetam (150 mg/kg), and the negative control received diazepam (2.5 mg/kg). Learning and memory were evaluated using the radial arm maze and the T-maze. Biomarkers of oxidative...
Source: Evidence-based Complementary and Alternative Medicine - August 14, 2020 Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research

Competitive Antagonism of Etomidate Action by Diazepam In Vitro GABA A Receptor and In Vivo Zebrafish Studies
Conclusions At micromolar concentrations and in the presence of flumazenil to inhibit allosteric modulationvia the classical benzodiazepine binding site of the GABAA receptor, diazepam acts as anin vitro andin vivo competitive etomidate antagonist.Editor ’s PerspectiveWhat We Already Know about This TopicDiazepam binds to the γ-aminobutyric acid type A (GABAA) receptor high-affinity extracellular benzodiazepine siteDiazepam can also bind to the GABAA receptor transmembrane etomidate siteIt is unknown whether diazepam or similar compounds can antagonize etomidateWhat This Article Tells Us That Is NewIn vitro and...
Source: Anesthesiology - August 13, 2020 Category: Anesthesiology Source Type: research

The role of hippocampal GABAA receptors on anxiolytic effects of Echium amoenum extract in a mice model of restraint stress.
This study examined whether GABA-ergic signaling is involved in the anxiolytic effects of EA in mice. Sixty BALB/c mice (25-30 g) were divided into six groups (n = 10) as follows: the (I) control group received 10 ml/kg normal saline (NS). In the stress groups, the animals underwent 14 consecutive days of restraint stress (RS), and received following treatments simultaneously; (II) RS + NS; (III) RS + Diaz (Diazepam); (IV) RS + EA; (V) RS + Flu (Flumazenil) + EA; (VI) RS + Flu + Diaz. Behavioral tests i...
Source: Molecular Biology Reports - August 10, 2020 Category: Molecular Biology Authors: Farajdokht F, Vosoughi A, Ziaee M, Araj-Khodaei M, Mahmoudi J, Sadigh-Eteghad S Tags: Mol Biol Rep Source Type: research

Neuro-behavioral Profile and Toxicity of the Essential Oil of Dorema ‎ammoniacum gum as an ...
In this study, we focused on the neuro-behavioral profile, toxicity, and‎possible mechanisms of action of‎ Dorema ammoniacum gum essential oil (DAG-EO). For this purpose, passive avoidance and Y-maze tests were performed to evaluate the potential effect‎of DAG-EO in the attenuation of memory impairment induced by 49 days administration of D-‎galactose and acute injection of scopolamine. Anticonvulsant and anti-nociceptive activities of DAG-EO were evaluated in the pentylenetetrazole and‎maximal electroshock-induced models of seizure and acetic acid-induced writhing tests, respectively.‎To find the p...
Source: Iranian Journal of Pharmaceutical Research - August 2, 2020 Category: Drugs & Pharmacology Source Type: research

Severe tetanus following ulcerated skin cancer: Case report
Rationale: Tetanus is usually caused by wound infection with Clostridium tetani after acute injuries. Skin cancer wound is a rarely reported cause of tetani infection. It is difficult to be diagnosed and mistaken for other brain lesions. Patient concerns: A 49-year-old man presenting with the only symptom of repeated convulsions was admitted to our department. He had an ulcerated skin cancer on the right buttock that had been excised in another hospital 1 month before admission, leaving the wound unhealed. He was suspected of having a metastatic brain tumor early, but exhibited a negative cranial CT-scan. Diagnosis: ...
Source: Medicine - July 31, 2020 Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research

Comparison of Different Liquid and Semisolid Vehicles Selected for Oral Administration of Pellets and Minitablets with Diazepam: In Vitro Investigation.
Abstract The acceptability and palatability of a dosage form are extremely important to improve patient compliance. Mixing oral solid dosage forms with food carriers is often necessary to ease swallowing and provide the taste-masking effect. The present research investigated how a liquid or semisolid carrier influences the disintegration time and drug dissolution rate of pellets and minitablets with diazepam. The disintegration of pellets and minitablets in liquid carriers (water, milk and apple juice) was determined using a texture analyser. Dissolution tests were performed for the dosage forms dispersed in gel v...
Source: AAPS PharmSciTech - July 31, 2020 Category: Drugs & Pharmacology Authors: Kotlowska H, Szymanska M, Sznitowska M Tags: AAPS PharmSciTech Source Type: research

Hypnotic activity of Capparis spinosa hydro-alcoholic extract in mice.
CONCLUSION: Our finding suggests that hydro-alcoholic extract of C. spinosa possesses hypnotic potential that may require further scientific investigations. PMID: 32718304 [PubMed - as supplied by publisher] (Source: Recent Patents on Food, Nutrition and Agriculture)
Source: Recent Patents on Food, Nutrition and Agriculture - July 30, 2020 Category: Food Science Tags: Recent Pat Food Nutr Agric Source Type: research

Lorazepam Versus Diazepam in the Management of Emergency Department Patients With Alcohol Withdrawal
Publication date: Available online 28 July 2020Source: Annals of Emergency MedicineAuthor(s): Frank X. Scheuermeyer, Isabelle Miles, Daniel J. Lane, Brian Grunau, Eric Grafstein, Igor Sljivic, Shayla Duley, Alec Yan, Ivan Chiu, Andrew Kestler, David Barbic, Jessica Moe, Amanda Slaunwhite, Seonaid Nolan, Lianping Ti, Grant Innes (Source: Annals of Emergency Medicine)
Source: Annals of Emergency Medicine - July 30, 2020 Category: Emergency Medicine Source Type: research

Generalized convulsive status epilepticus after retrograde type A aortic dissection surgery.
CONCLUSION: Generalized convulsive status epilepticus should be alert for avoiding delay in the rehabilitation particularly after aortic dissection surgery. Under the good condition of ventilation, combining morphine with midazolam or diazepam can more effectively relieve the symptoms. PMID: 32723152 [PubMed - as supplied by publisher] (Source: Perfusion)
Source: Perfusion - July 29, 2020 Category: Cardiovascular & Thoracic Surgery Authors: Li Y, Wu Q, Shi H, Chen D, Zhang C Tags: Perfusion Source Type: research

Apremilast regulates acute effects of ethanol and other GABAergic drugs via protein kinase A-dependent signaling.
Abstract Phosphodiesterase type 4 (PDE4) inhibitors prevent hydrolysis of cyclic adenosine monophosphate and increase protein kinase A (PKA)-mediated phosphorylation. PDE4 inhibitors also regulate responses to ethanol and GABAergic drugs. We investigated mechanisms by which the PDE4 inhibitor, apremilast, regulates acute effects of ethanol and GABAergic drugs in male and female mice. Apremilast prolonged the sedative-hypnotic effects of gaboxadol, zolpidem, and propofol but did not alter etomidate effects, and unexpectedly shortened the sedative-hypnotic effects of diazepam. Apremilast prolonged rotarod ataxia ind...
Source: Neuropharmacology - July 28, 2020 Category: Drugs & Pharmacology Authors: Blednov YA, Borghese CM, Dugan MP, Pradhan S, Thodati TM, Kichili NR, Harris RA, Messing RO Tags: Neuropharmacology Source Type: research

Psychosocial interventions for conversion and dissociative disorders in adults.
ash;gaard U Abstract BACKGROUND: Conversion and dissociative disorders are conditions where people experience unusual neurological symptoms or changes in awareness or identity. However, symptoms and clinical signs cannot be explained by a neurological disease or other medical condition. Instead, a psychological stressor or trauma is often present. The symptoms are real and can cause significant distress or problems with functioning in everyday life for the people experiencing them. OBJECTIVES: To assess the beneficial and harmful effects of psychosocial interventions of conversion and dissociative disorders i...
Source: Cochrane Database of Systematic Reviews - July 17, 2020 Category: General Medicine Authors: Ganslev CA, Storebø OJ, Callesen HE, Ruddy R, Søgaard U Tags: Cochrane Database Syst Rev Source Type: research

Involvement of the Benzodiazepine Site in the Anticonvulsant Activity of Tapinanthus globiferus against Pentylenetetrazole-induced Seizures in Mice
Planta Med DOI: 10.1055/a-1209-1254 Tapinanthus globiferus is often referred to as an all-purpose herb for the treatment of stroke and epilepsy. The present study investigates the anticonvulsant effect of methanolic leaf extract, active fractions, and lupeol (isolate) of Tapinanthus globiferus in mice as well as the underlying mechanisms. Following phytochemical studies of T. globiferus, preliminary assays were performed to evaluate MLE-induced toxic effect and behavioral changes. The pentylenetetrazol (70 mg/kg, i. p.)-induced seizure was evaluated in mice that were pretreated orally with vehicle 10 mL/...
Source: Planta Medica - July 15, 2020 Category: Drugs & Pharmacology Authors: Elusiyan, Christianah A. Faria, Ana Luiza Gon çalves Mendes, Ane Emanuelle Queiroga Silva, Irans é Oliveira Martins, Jos é Luis Rodrigues Rosa, Daniel Alves Pedrino, Gustavo Rodrigues Costa, Elson Alves Ibrahim, Mohamed Ali Zjawiony, Jordan K. Fajemiro Tags: Original Papers Source Type: research

Genes, Vol. 11, Pages 774: Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED)
Andrea Tipold Tosso Leeb Four female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress, were investigated in a retrospective multi-center investigation aiming to characterize the clinical phenotype and its underlying molecular etiology. Three dogs were closely related and their pedigree suggested autosomal dominant inheritance. Laboratory diagnostic findings included mild lactic acidosis and lactaturia, mild intermittent serum creatine kinase (CK) elevation and hypoglycemia. Electrophysiological tests and magnetic resonance imaging of the brain were unremarkable. A m...
Source: Genes - July 9, 2020 Category: Genetics & Stem Cells Authors: Jasmin Nessler Petra Hug Paul J. J. Mandigers Peter A. J. Leegwater Vidhya Jagannathan Anibh M. Das Marco Rosati Kaspar Matiasek Adrian C. Sewell Marion Kornberg Marina Hoffmann Petra Wolf Andrea Fischer Andrea Tipold Tosso Leeb Tags: Article Source Type: research

Therapeutic Effect of Berberine on Insomnia Rats by ErbB Signaling Pathway.
CONCLUSIONS These results suggest that berberine can alleviate insomnia in rats through a neuroprotective effect and improved metabolic level. Berberine has great potential in treatment of insomnia and might have better clinical significance. PMID: 32623439 [PubMed - as supplied by publisher] (Source: Medical Science Monitor)
Source: Medical Science Monitor - July 6, 2020 Category: Research Tags: Med Sci Monit Source Type: research

Metabolic and psychiatric effects of acyl coenzyme A binding protein (ACBP)/diazepam binding inhibitor (DBI)
Cell Death & Disease, Published online: 06 July 2020; doi:10.1038/s41419-020-2716-5Metabolic and psychiatric effects of acyl coenzyme A binding protein (ACBP)/diazepam binding inhibitor (DBI) (Source: Cell death and disease)
Source: Cell death and disease - July 6, 2020 Category: Internal Medicine Authors: Adrien Joseph St éphanie Moriceau Valentina Sica Gerasimos Anagnostopoulos Jonathan Pol Isabelle Martins Antoine Lafarge Maria Chiara Maiuri Marion Leboyer Josephine Loftus Frank Bellivier Raoul Belzeaux Fabrice Berna Bruno Etain Delphine Capdevielle Phi Source Type: research

Levetiracetam vs. Fosphenytoin for Second-Line Treatment of Status Epilepticus: Propensity Score Matching Analysis Using a Nationwide Inpatient Database
Conclusion: Levetiracetam was related to significantly reduced vasopressor use on the day of admission than that found for fosphenytoin, in adult status epilepticus. (Source: Frontiers in Neurology)
Source: Frontiers in Neurology - July 2, 2020 Category: Neurology Source Type: research

Therapeutic Interventions for Adjustment Disorder: A Systematic Review
Conclusions: Psychotherapy seems indicated for mildly symptomatic adjustment disorder. Given the fact that adjustment disorder with severe symptoms is associated with a high risk of suicidal ideation and suicide attempts, clinicians must consider the potential benefit of using psychotropic agents such as benzodiazepines, antidepressants, or etifoxine. (Source: American Journal of Therapeutics)
Source: American Journal of Therapeutics - July 1, 2020 Category: Drugs & Pharmacology Tags: Systematic Review and Clinical Guidelines Source Type: research

Acute poisoning from substance abuse of benzodiazepines.
We describe cases of acute poisoning related to substance abuse of benzodiazepines in patients at the main A&E clinic in Oslo. MATERIAL AND METHOD: We included all patients treated for substance abuse poisoning with benzodiazepines and/or z-hypnotics at the Oslo Accident and Emergency Outpatient Clinic from 1 October 2013 to 30 September 2015. The patients were found through a retrospective review of the A&E clinic's registers. Data were taken from patient records. Diagnosis of the toxic agent was based on the attending doctor's recorded clinical evaluation. RESULTS: Of 1 037 cases, 787 (76 %) were m...
Source: Tidsskrift for den Norske Laegeforening - June 30, 2020 Category: General Medicine Authors: Andersson JA, Brekke M, Vallersnes OM Tags: Tidsskr Nor Laegeforen Source Type: research

Synthesis and Evaluation of Anticonvulsant Activity of Schiff Base of 1,4-Benzodiazepine Amine.
Abstract A variety of 1,4-benzodiazepine azomethines (3a-n) and 1,4-benzodiazepine benzamide (4) were prepared, characterized and evaluated for the anticonvulsant activity in the rat using picrotoxin-induced seizure model. The prepared 1,4-benzodiazepine azomethine derivative emerged potentially anticonvulsant molecular scaffolds exemplified by compounds, 7-(4-nitrophenyl)methyleneamino-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one (3c), 7-[4-(dimethylamino)phenyl]methyleneamino-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one (3e), 7-[(4-bromo-2,6-difluoro-phenyl)methyleneamino]-5-phenyl-1,3-dihydro-1,4-benzodiazepin-...
Source: Chemistry and Biodiversity - June 29, 2020 Category: Biochemistry Authors: Gawande MB, Nilkanth PR, Ghorai S, S A, Dhawale K, Shelke S, Ahamad T Tags: Chem Biodivers Source Type: research

The adenosine A1 receptor agonist WAG 994 suppresses acute kainic acid-induced status epilepticus in vivo.
Abstract Status epilepticus (SE) is a neurological emergency characterized by continuous seizure activity lasting longer than 5 min, often with no recovery between seizures (Trinka et al., 2015). SE is refractory to benzodiazepine and second-line treatments in about 30% cases. Novel treatment approaches are urgently needed as refractory SE is associated with mortality rates of up to 70%. Robust adenosinergic anticonvulsant effects have been known for decades, but translation into seizure treatments was hampered by cardiovascular side effects. However, the selective adenosine A1 receptor agonist SDZ WAG 994 (WAG)...
Source: Neuropharmacology - June 29, 2020 Category: Drugs & Pharmacology Authors: Klaft ZJ, Duerrwald LM, Gerevich Z, Dulla CG Tags: Neuropharmacology Source Type: research

Anxiolytic-like effects of Moringa oleifera in Swiss mice.
This study investigated the anxiolytic-like effects of crude organic fractions of M. oleifera leaves in different behavioral paradigms that evaluate anxiety in mice. To this end, mice were administered with crude extracts (500 mg/kg, p.o.) and/or diazepam (2 mg/kg, p.o.), and submitted to behavioral tests. In the open-field test, the number of square field cross, grooming and rearing were calculated, while in light-dark and swing test were, respectively, the time spent in dark portion and number of swings. Each test was performed for 3 min. M. oleifera leaf methanol and n-hexane extracts elicited an anxiolytic-like effect ...
Source: Cellular and Molecular Biology - June 26, 2020 Category: Molecular Biology Tags: Cell Mol Biol (Noisy-le-grand) Source Type: research

Ascorbic acid antagonizes the sedative effect of diazepam possibly through inhibition of GABA(A ρ₁) and GABA(B1) receptors.
In conclusion, DZP is a GABA receptor agonist and AA may reverse DZP-mediated sedative effects in a non-competitive binding fashion in mice through inhibition of GABA(Aρ₁) and GABA(B1) receptors. PMID: 32583769 [PubMed - in process] (Source: Cellular and Molecular Biology)
Source: Cellular and Molecular Biology - June 26, 2020 Category: Molecular Biology Tags: Cell Mol Biol (Noisy-le-grand) Source Type: research

Suvorexant, a dual orexin receptor antagonist, protected seizure through interaction with GABAA ...
In this study, the effects of suvorexant (orexin receptor antagonist) on pentylenetetrazol (PTZ) and maximal electroshock (MES)-induced seizure were investigated. Mice were divided into 5 groups of six animals each including normal saline (10 ml/kg), diazepam (2 mg/kg) and suvorexant (50, 100 and 200 mg/kg) groups. In PTZ test, the latency to first minimal clonic seizure (MCS), latency to the first generalized tonic–clonic seizures (GTCS), total duration of seizure and also protection against mortality were evaluated. In MES, the hind limb tonic extension (HLTE) and the protection against mortality were recorded. In ...
Source: Iranian Journal of Pharmaceutical Research - June 21, 2020 Category: Drugs & Pharmacology Source Type: research

Biochemical and toxicological effect of diazepam in stress-induced cardiac dysfunctions
Publication date: Available online 18 June 2020Source: Toxicology ReportsAuthor(s): Fahad A. Al-Abassi, Vikas Kumar, Firoz Anwar (Source: Toxicology Reports)
Source: Toxicology Reports - June 19, 2020 Category: Toxicology Source Type: research

Anaesthesia/analgesia for manual removal of retained placenta.
CONCLUSIONS: There is insufficient evidence from one small study to evaluate the effectiveness and safety of anaesthesia or analgesia during the manual removal of a retained placenta. The quality of the available evidence was very low. We downgraded based on issues of limitations in study design (risk of bias) and imprecision (single study with small sample size, few or no events, and wide confidence intervals). There is a need for well-designed, multi-centre, randomised, controlled trials to evaluate the effectiveness and safety of different types of anaesthesia and analgesia during manual removal of a retained placenta. ...
Source: Cochrane Database of Systematic Reviews - June 12, 2020 Category: General Medicine Authors: Kongwattanakul K, Rojanapithayakorn N, Laopaiboon M, Lumbiganon P Tags: Cochrane Database Syst Rev Source Type: research

Cannabis and Multiple Sclerosis.
Authors: Fragoso YD, Carra A, Macias MA Abstract INTRODUCTION: Patients with multiple sclerosis (MS) may suffer from spasticity and pain during their disease course. Baclofen, dantrolene, diazepam and gabapentin have been used as first-line options to treat these conditions, with modest results. Medical use of marijuana smoking has bypassed traditional clinical trials and has been legalized as a therapeutic option for MS-related spasticity and pain in some countries. Cannabis-derived drugs have been tested and approved for medical use. AREAS COVERED: With the development of nabiximols by the pharmaceutical industry...
Source: Expert Review of Neurotherapeutics - June 10, 2020 Category: Neurology Tags: Expert Rev Neurother Source Type: research

Competitive Antagonism of Etomidate Action by Diazepam In Vitro GABA A Receptor and In Vivo Zebrafish Studies
ConclusionsAt micromolar concentrations and in the presence of flumazenil to inhibit allosteric modulationvia the classical benzodiazepine binding site of the GABAA receptor, diazepam acts as anin vitro andin vivo competitive etomidate antagonist.Editor ’s PerspectiveWhat We Already Know about This TopicDiazepam binds to the γ-aminobutyric acid type A (GABAA) receptor high-affinity extracellular benzodiazepine siteDiazepam can also bind to the GABAA receptor transmembrane etomidate siteIt is unknown whether diazepam or similar compounds can antagonize etomidateWhat This Article Tells Us That Is NewIn vitro andi...
Source: Anesthesiology - June 10, 2020 Category: Anesthesiology Source Type: research

Intentional Hydroxychloroquine Overdose Treated with High-Dose Diazepam: an Increasing Concern in the COVID-19 Pandemic.
DISCUSSION: Hydroxychloroquine toxicity is rare but projected to increase in frequency given its selection as a potential modality to treat COVID-19 disease. It is important for clinicians to recognize the unique effects of hydroxychloroquine poisoning and initiate appropriate emergency maneuvers to improve the outcomes in these patients. PMID: 32514696 [PubMed - as supplied by publisher] (Source: Journal of Medical Toxicology)
Source: Journal of Medical Toxicology - June 8, 2020 Category: Toxicology Authors: Chai PR, Ferro EG, Kirshenbaum JM, Hayes BD, Culbreth SE, Boyer EW, Erickson TB Tags: J Med Toxicol Source Type: research

Evaluation of a Novel Protocol for Assessment and Treatment of Alcohol Withdrawal Syndrome in Psychiatric Inpatients.
Abstract BACKGROUND AND OBJECTIVES: Despite the high incidence of alcohol withdrawal syndrome (AWS) in psychiatric inpatients, standardized methods for assessing and treating AWS have been studied only once before in this population. We evaluated a novel AWS assessment and treatment protocol designed for psychiatric inpatients. METHODS: This retrospective cohort study evaluated outcomes before and after implementation of the protocol. We collected consecutive data on patients (N = 138) admitted to inpatient psychiatric units at a single center. Participants were patients admitted for nonsubstanc...
Source: American Journal on Addictions - June 3, 2020 Category: Addiction Authors: Butterfield M, Thorne-Humphrey L, Suzuki J, Herschenhous N Tags: Am J Addict Source Type: research

Tu1092 OPTIMAL SEDATION FOR THE GASTROINTESTIINAL ENDOSCOPY WITH THE COMBINATION OF INTERMEDIATE - ACTION AND RAPID- ACTION AGENT
Since 1989, we have performed the gastrointestinal endoscopy with sedation of 2 agents combination (diazepam/thiopental sodium). In 1997, we changed diazepam to midazolam in order to decrease the risk of respiratory depression. Since 2010, we have used propofol instead of thiopental sodium in order to decrease the risk of cough from sputum. (Source: Gastrointestinal Endoscopy)
Source: Gastrointestinal Endoscopy - June 1, 2020 Category: Gastroenterology Authors: MIDAZOLAM PREDOMINANT/PROPOFOL VERSUS MIDAZORM/PROPOFOL PREDOMINANT, Hirotsugu Ohara Tags: Poster abstracts Source Type: research

Suvorexant, a dual orexin receptor antagonist, protected seizure through interaction with GABAA ...
In this study, the effects of suvorexant (orexin receptor antagonist) on pentylenetetrazol (PTZ) and maximal electroshock (MES)-induced seizure were investigated. Mice were divided into 5 groups of six animals each including normal saline (10 ml/kg), diazepam (2 mg/kg) and suvorexant (50, 100 and 200 mg/kg) groups. In PTZ test, the latency to first minimal clonic seizure (MCS), latency to the first generalized tonic–clonic seizures (GTCS), total duration of seizure and also protection against mortality were evaluated. In MES, the hind limb tonic extension (HLTE) and the protection against mortality were recorded. In ...
Source: Iranian Journal of Pharmaceutical Research - May 31, 2020 Category: Drugs & Pharmacology Source Type: research