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Dantrolene

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https://www.readbyqxmd.com/read/29314443/ryanodine-receptor-inhibition-by-dantrolene-effectively-suppresses-ventricular-arrhythmias-in-an-ex-vivo-model-of-long-qt-syndrome
#1
Gerrit Frommeyer, Julius Krawczyk, Christian Ellermann, Nils Bögeholz, Simon Kochhäuser, Dirk G Dechering, Michael Fehr, Lars Eckardt
AIMS: A significant antiarrhythmic potential of ryanodine receptor inhibition was reported in experimental studies. The aim of the present study was to assess potential antiarrhythmic effects of dantrolene in an experimental whole-heart model of drug-induced long-QT syndrome (LQTS). METHODS: In 12 isolated rabbit hearts long-QT-2-syndrome was simulated by infusion of erythromycin (300μM). 12 rabbit hearts were treated with veratridine (0.5μM) to mimic long-QT-3-syndrome...
January 4, 2018: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/29237755/differential-contribution-of-ca2-sources-to-day-and-night-bk-current-activation-in-the-circadian-clock
#2
Joshua P Whitt, Beth A McNally, Andrea L Meredith
Large conductance K+ (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca2+ (Ca2+i). To enable this regulation, BK channels functionally couple to both voltage-gated Ca2+ channels (VGCCs) and channels mediating Ca2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca2+i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca2+i are reduced...
December 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29216442/lycopene-depresses-glutamate-release-through-inhibition-of-voltage-dependent-ca-sup-2-sup-entry-and-protein-kinase-c-in-rat-cerebrocortical-nerve-terminals
#3
Cheng-Wei Lu, Chi-Feng Hung, Wei-Horng Jean, Tzu-Yu Lin, Shu-Kuei Huang, Su Jane Wang
Lycopene is a natural dietary carotenoid which was reported to exhibit neuroprotective profile. Considering that excitotoxicity and cell death induced by glutamate are involved in many brain disorders, the effect of lycopene on glutamate release in rat cerebrocortical nerve terminals and the possible mechanism involved in such effect was investigated. We observed here that lycopene inhibited 4-aminopyridine (4-AP)-evoked glutamate release and intrasynaptosomal Ca <sup>2+<sup> concentration elevation...
December 7, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29214114/calcium-dysregulation-in-alzheimer-s-disease-a-target-for-new-drug-development
#4
Yong Wang, Yun Shi, Huafeng Wei
Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia among aged people whose population is rapidly increasing. AD not only seriously affects the patient's physical health and quality of life, but also adds a heavy burden to the patient's family and society. It is urgent to understand AD pathogenesis and develop the means of prevention and treatment. AD is a chronic devastating neurodegenerative disease without effective treatment. Current approaches for management focus on helping patients relieve or delay the symptoms of cognitive dysfunction...
August 2017: Journal of Alzheimer's Disease and Parkinsonism
https://www.readbyqxmd.com/read/29155254/association-of-riluzole-and-dantrolene-improves-significant-recovery-after-acute-spinal-cord-injury-in-rats
#5
Bernardo De Caro Martins, Bruno Benetti Junta Torres, Karen Maciel de Oliveira, Mario Sergio Lavor, Carla Maria Osório, Fabiola Bono Fukushima, Isabel Rodrigues Rosado, Eliane Gonçalves de Melo
BACKGROUND CONTEXT: Damage to the spinal cord can result in irreversible impairment or complete loss of motor, sensory, and autonomic functions. Riluzole and dantrolene have been shown to provide neuroprotection by reducing neuronal apoptosis after brain and spinal cord injury (SCI) in several animal models of neurologic disorders. As these drugs protect the injured spinal cord through different mechanisms, we investigated the cumulative effects of riluzole and dantrolene. PURPOSE: This study aimed to investigate the neuroprotective efficacy of the combined administration of riluzole and dantrolene in experimental thoracic SCI...
November 15, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/29057139/comparison-study-of-voltammetric-behavior-of-muscle-relaxant-dantrolene-sodium-on-silver-solid-amalgam-and-bismuth-film-electrodes
#6
Renáta Šelešovská, Pavlína Martinková, Michaela Štěpánková, Tomáš Navrátil, Jaromíra Chýlková
Voltammetric behavior of muscle relaxant dantrolene sodium (DAN) was studied and the voltammetric methods for its determination using polished and mercury meniscus modified silver solid amalgam electrodes (p-AgSAE and m-AgSAE) as well as using bismuth film electrode (BiFE, ex situ plating on GCE) have been proposed. These working electrodes represent the most commonly used alternatives to mercury ones which come wrongfully into disfavor because of alleged toxicity of mercury. Within this work, the obtained results of DAN determination have been completed by corresponding statistical parameters and also some electrochemical characteristics of AgSAEs and BiFE were assessed, especially in comparison with the mercury electrodes...
2017: Journal of Analytical Methods in Chemistry
https://www.readbyqxmd.com/read/29027245/epac-induced-ryanodine-receptor-type-2-activation-inhibits-sodium-currents-in-atrial-and-ventricular-murine-cardiomyocytes
#7
Haseeb Valli, Shiraz Ahmad, Sujan Sriharan, Lydia D Dean, Andrew A Grace, Kamalan Jeevaratnam, Hugh R Matthews, Christopher L-H Huang
Acute RyR2 activation by exchange protein directly activated by cAMP (Epac) reversibly perturbs myocyte Ca(2+) homeostasis, slows myocardial action potential conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies, preserving in vivo extracellular and intracellular conditions, investigated Na(+) current in intact cardiomyocytes in murine atrial and ventricular preparations following Epac activation. Depolarising steps to varying test voltages activated typical voltage-dependent Na(+) currents...
October 12, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28972685/effects-of-manipulating-tetanic-calcium-on-the-curvature-of-the-force-velocity-relationship-in-isolated-rat-soleus-muscles
#8
A M Kristensen, O B Nielsen, K Overgaard
AIM: In dynamically contracting muscles, increased curvature of the force-velocity relationship contributes to the loss of power during fatigue. It has been proposed that fatigue-induced reduction in [Ca(++) ]i causes this increased curvature. However, earlier studies on single fibers have been conducted at low temperatures. Here, we investigated the hypothesis that curvature is increased by reductions in tetanic [Ca(++) ]i in isolated skeletal muscle at near-physiological temperatures...
October 3, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28880093/quantification-of-transporter-and-receptor-proteins-in-dog-brain-capillaries-and-choroid-plexus-relevance-for-the-distribution-in-brain-and-csf-of-selected-bcrp-and-p-gp-substrates
#9
Clemens Braun, Atsushi Sakamoto, Holger Fuchs, Naoki Ishiguro, Shinobu Suzuki, Yunhai Cui, Klaus Klinder, Michitoshi Watanabe, Tetsuya Terasaki, Achim Sauer
Transporters at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) play a pivotal role as gatekeepers for efflux or uptake of endogenous and exogenous molecules. The protein expression of a number of them has already been determined in the brains of rodents, nonhuman primates, and humans using quantitative targeted absolute proteomics (QTAP). The dog is an important animal model for drug discovery and development, especially for safety evaluations. The purpose of the present study was to clarify the relevance of the transporter protein expression for drug distribution in the dog brain and CSF...
October 2, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28872668/efficacy-of-oral-pharmacological-treatments-in-dyskinetic-cerebral-palsy-a-systematic-review
#10
REVIEW
Riccardo Masson, Emanuela Pagliano, Giovanni Baranello
AIM: To evaluate the actual evidence of efficacy of oral pharmacological treatments in the management of dyskinetic cerebral palsy (CP). METHOD: A systematic review was performed according to the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Articles were searched for in PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, Database of Reviews of Effectiveness, OTSeeker, Physiotherapy Evidence Database, REHABDATA, and ClinicalTrials...
December 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/28820004/drug-induced-liver-injury-in-children-clinical-observations-animal-models-and-regulatory-status
#11
Qiang Shi, Xi Yang, James J Greenhaw, Alec Thomas Salminen, Gary M Russotti, William F Salminen
Drug-induced liver injury in children (cDILI) accounts for about 1% of all reported adverse drug reactions throughout all age groups, less than 10% of all clinical DILI cases, and around 20% of all acute liver failure cases in children. The overall DILI susceptibility in children has been assumed to be lower than in adults. Nevertheless, controversial evidence is emerging about children's sensitivity to DILI, with children's relative susceptibility to DILI appearing to be highly drug-specific. The culprit drugs in cDILI are similar but not identical to DILI in adults (aDILI)...
September 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28808649/the-effect-of-a-single-dose-dantrolene-in-patients-with-vasospasm-following-aneurysmal-subarachnoid-hemorrhage
#12
Masih Sabouri, Mahmood Momeni, Fariborz Khorvash, Majid Rezvani, Homayon Tabesh
BACKGROUND: Cerebral vasospasm is a prolonged, occasionally severe, but reversible narrowing of the cerebral arteries that begins 3 to 5 days after the hemorrhage becomes maximal at 14 days. This study is designed to evaluate the effect of dantrolene on the reduction of vasospasm following aneurysmal subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: This randomized controlled clinical trial was conducted on 32 patients with proven aneurysms in AL-Zahra hospital during 2011-2013...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28752347/-prolonged-neuroleptic-malignant-syndrome-after-haloperidol-injection
#13
N Wystub, S Heymel, M Fritzenwanger, P C Schulze, R Pfeifer
Neuroleptic malignant syndrome (NMS) is a rare disorder caused by drug-induced dopamine-receptor-blockage or low dopamine concentration in the brain. It is a severe reaction to neuroleptic drugs in antipsychotic therapy. Symptoms in NMS typically consist of fever, muscle rigidity and cognitive changes; laboratory findings include elevated infectious disease markers and creatine kinase as well as signs of rhabdomyolysis. To differentiate NMS from other malignant hyperthermia syndromes identifying the offending drug and clinical history are essential...
July 27, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28717166/targeting-cellular-calcium-homeostasis-to-prevent-cytokine-mediated-beta-cell-death
#14
Amy L Clark, Kohsuke Kanekura, Zeno Lavagnino, Larry D Spears, Damien Abreu, Jana Mahadevan, Takuya Yagi, Clay F Semenkovich, David W Piston, Fumihiko Urano
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697029/malignant-hyperthermia-in-a-morbidly-obese-patient-depletes-community-dantrolene-resources-a-case-report
#15
Fabio Magistris, Jonathan Gamble
During resection of a duodenal carcinoid tumor, a 28-year-old morbidly obese woman developed suspected malignant hyperthermia. This hypermetabolic state posed a diagnostic challenge given the similar intraoperative presentation of carcinoid crisis and malignant hyperthermia. The patient's weight posed therapeutic challenges as massive doses and prolonged administration of dantrolene were required that quickly depleted the available supply. Current dantrolene dosing recommendations are based on actual body weight despite a paucity of literature in obese patients...
November 1, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28687594/reduced-threshold-for-store-overload-induced-ca-2-release-is-a-common-defect-of-ryr1-mutations-associated-with-malignant-hyperthermia-and-central-core-disease
#16
COMPARATIVE STUDY
Wenqian Chen, Andrea Koop, Yingjie Liu, Wenting Guo, Jinhong Wei, Ruiwu Wang, David H MacLennan, Robert T Dirksen, Sui Rong Wayne Chen
Mutations in the skeletal muscle ryanodine receptor (RyR1) cause malignant hyperthermia (MH) and central core disease (CCD), whereas mutations in the cardiac ryanodine receptor (RyR2) lead to catecholaminergic polymorphic ventricular tachycardia (CPVT). Most disease-associated RyR1 and RyR2 mutations are located in the N-terminal, central, and C-terminal regions of the corresponding ryanodine receptor (RyR) isoform. An increasing body of evidence demonstrates that CPVT-associated RyR2 mutations enhance the propensity for spontaneous Ca(2+) release during store Ca(2+) overload, a process known as store overload-induced Ca(2+) release (SOICR)...
August 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28660414/-stocks-of-dantrolene-in-anesthesia-and-intensive-care-units-in-germany-nationwide-online-survey-with-1673-participants
#17
E Pfenninger, S Heiderich, W Klingler
BACKGROUND: A malignant hyperthermia (MH) crisis is a potentially fatal complication in anesthesia and intensive care units (ICU). Rapid administration and adequate dosage of dantrolene is the only known effective pharmacological and causal treatment of an MH crisis. International anesthesiology societies recommend an initial dose of 2.0-2.5 mg/kg body weight (BW). The necessary total dosage should be titrated up to 10 mg/kg BW depending on the effectiveness. OBJECTIVE: The goal of this study was an analysis of the stocking situation of dantrolene in Germany...
October 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/28630284/differential-interaction-of-dantrolene-glafenine-nalidixic-acid-and-prazosin-with-human-organic-anion-transporters-1-and-3
#18
Birgitta C Burckhardt, Maja Henjakovic, Yohannes Hagos, Gerhard Burckhardt
In renal proximal tubule cells, the organic anion transporters 1 and 3 (OAT1 and OAT3) in the basolateral membrane and the multidrug resistance-associated protein 4 (MRP4) in the apical membrane share substrates and co-operate in renal drug secretion. We hypothesized that recently identified MRP4 inhibitors dantrolene, glafenine, nalidixic acid, and prazosin also interact with human OAT1 and/or OAT3 stably transfected in human embryonic kidney 293 cells. These four drugs were tested as possible inhibitors of p-[(3)H]aminohippurate (PAH) and [(14)C]glutarate uptake by OAT1, and of [(3)H]estrone-3-sulfate (ES) uptake by OAT3...
September 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28619610/forecasting-gastrointestinal-precipitation-and-oral-pharmacokinetics-of-dantrolene-in-dogs-using-an-in-vitro-precipitation-testing-coupled-with-in-silico-modeling-and-simulation
#19
Atsushi Kambayashi, Jennifer B Dressman
The aim of the current research was to determine the precipitation kinetics of dantrolene sodium using canine biorelevant in vitro testing and to model the precipitation kinetics by appropriately coupling the data with an in silico tool adapted for dogs. The precipitation profiles of dantrolene sodium solutions were obtained with the in vitro paddle apparatus at a revolution rate of 50rpm. The in silico prediction tool was designed using STELLA software and the predicted plasma concentration profiles of dantrolene using the in vitro precipitation data were compared with the observed in vivo pharmacokinetics in beagle dogs...
October 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28596111/high-fat-diet-disrupts-endoplasmic-reticulum-calcium-homeostasis-in-the-rat-liver
#20
Emily S Wires, Kathleen A Trychta, Susanne Bäck, Agnieszka Sulima, Kenner C Rice, Brandon K Harvey
BACKGROUND & AIMS: Disruption to endoplasmic reticulum (ER) calcium homeostasis has been implicated in obesity, however, the ability to longitudinally monitor ER calcium fluctuations has been challenging with prior methodologies. We recently described the development of a Gaussia luciferase (GLuc)-based reporter protein responsive to ER calcium depletion (GLuc-SERCaMP) and investigated the effect of a high fat diet on ER calcium homeostasis. METHODS: A GLuc-based reporter cell line was treated with palmitate, a free fatty acid...
July 17, 2017: Journal of Hepatology
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