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Angela Regina, David Lee, Payal Sud, Diana Crevi
No abstract text is available yet for this article.
December 2016: Pediatric Emergency Care
Wook Kim, Hyun Soo Park, Byung Seok Moon, Byung Chul Lee, Sang Eun Kim
INTRODUCTION: We measured the tiagabine-induced enhancement of the GABAA receptor's affinity for benzodiazepine ligands ("GABA shift") using [(18)F]flumazenil (FMZ) PET with preclinical application of bolus plus constant infusion (B/I). Differences in quantified results of [(18)F]FMZ binding were compared to that of [(18)F]FMZ PET with single bolus injection (SB). MATERIALS AND METHODS: Sprague-Dawley rats underwent [(18)F]FMZ PET scans with B/I, which consisted of baseline and "GABA shift" sessions in a scan, or scans with SB one week apart...
November 4, 2016: Nuclear Medicine and Biology
Mark Donaldson, Jason H Goodchild
Though uncommon, medical emergencies in the dental office are harrowing occurrences that can be the result of adverse drug reactions. Pharmacological antagonists have been developed for administration as reversal agents in emergency situations in which patients may have an untoward effect, typically caused by too much medication. Dental practitioners should be familiar with these agents to keep patients safe and help mitigate drug-induced medical emergencies. This article reviews the pharmacokinetic and pharmacodynamic principles of pharmacological antagonists; it emphasizes six specific reversal agents as they relate to the clinical practice of dentistry: naloxone, flumazenil, epinephrine, diphenhydramine, phentolamine, and atropine...
November 2016: Compendium of Continuing Education in Dentistry
Mikael Palner, Corinne Beinat, Sam Banister, Francesca Zanderigo, Jun Hyung Park, Bin Shen, Trine Hjoernevik, Jae Ho Jung, Byung Chul Lee, Sang Eun Kim, Lawrence Fung, Frederick T Chin
BACKGROUND: The availability of GABAA receptor binding sites in the brain can be assessed by positron emission tomography (PET) using the radioligand, [(18)F]flumazenil. However, the brain uptake and binding of this PET radioligand are influenced by anesthetic drugs, which are typically needed in preclinical imaging studies and clinical imaging studies involving patient populations that do not tolerate relatively longer scan times. The objective of this study was to examine the effects of anesthesia on the binding of [(18)F]flumazenil to GABAA receptors in mice...
December 2016: EJNMMI Research
Camille Cohier, Lucie Chevillard, Sophie Salle, Patricia Risède, Olivier Roussel, Bruno Mégarbane
Respiratory depression and fatalities have been attributed to ethanol/buprenorphine combination in drug addicts maintained with buprenorphine/naloxone or buprenorphine alone. The exact mechanisms of the ethanol/buprenorphine interaction and the contribution to the toxicity of norbuprenorphine, the main buprenorphine metabolite with respiratory depressant properties are unknown. We investigated the sedative and plethsymographic effects resulting from the co-administration of intragastric ethanol (3g/kg) and intravenous buprenorphine (30mg/kg) in Sprague-Dawley rats...
November 1, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Antonia Di Mola, Elena Gatta, Carmen Petronzi, Aroldo Cupello, Paolo De Caprariis, Mauro Robello, Antonio Massa, Rosanna Filosa
A focused N-substituted 3-(2-piperazin-1-yl-2-oxoethyl)-2-(pyridin-2-yl)iso-indolin-1-ones small library was synthesized for modulation of GABA-A receptor function and compared to Zopiclone for the ability to increase GABA-activated chloride currents. All compounds were tested for their effects on GABA-activated chloride currents in rat cerebellar granule cells by use of the whole-cell patch clamp technique. Electrophysiological studies on cultured cerebellar granule cells revealed 3-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2-(5-nitropyridin-2-yl)iso-indolin-1-one (Id) as a partial agonist displaying 34% increase of the 10μM GABA evoked peak chloride currents, antagonized by flumazenil...
September 15, 2016: Bioorganic & Medicinal Chemistry Letters
David Franklin Niedrig, Liesa Hoppe, Sarah Mächler, Heike Russmann, Stefan Russmann
OBJECTIVE: Benzodiazepines and "Z-drug" GABA-receptor modulators (BDZ) are among the most frequently used drugs in hospitals. Adverse drug events (ADE) associated with BDZ can be the result of preventable medication errors (ME) related to dosing, drug interactions and comorbidities. The present study evaluated inpatient use of BDZ and related ME and ADE. METHODS: We conducted an observational study within a pharmacoepidemiological database derived from the clinical information system of a tertiary care hospital...
2016: PloS One
Marina Hodolic, Raffi Topakian, Robert Pichler
BACKGROUND: Epilepsy is a neurological disorder characterized by epileptic seizures as a result of excessive neuronal activity in the brain. Approximately 65 million people worldwide suffer from epilepsy; 20-40% of them are refractory to medication therapy. Early detection of disease is crucial in the management of patients with epilepsy. Correct localization of the ictal onset zone is associated with a better surgical outcome. The modern non-invasive techniques used for structural-functional localization of the seizure focus includes electroencephalography (EEG) monitoring, magnetic resonance imaging (MRI), single photon emission tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT)...
September 1, 2016: Radiology and Oncology
Zarah Jordahn, Cheme Andersen, Anne Marie Roust Aaberg, Frank Christian Pott
We describe the care for an elderly woman who was admitted to the intensive care unit (ICU) to receive noninvasive ventilation for acute exacerbation of chronic obstructive pulmonary disease. After administration of the sleeping pill zopiclone, a nonbenzodiazepine receptor agonist (NBRA), the patient became agitated and was confused, a possible paradoxical reaction to benzodiazepines. These symptoms were immediately resolved after treatment with flumazenil, usually used to reverse the adverse effects of benzodiazepines or NBRAs and to reverse paradoxical reactions to benzodiazepines...
2016: Case Reports in Critical Care
Thomas Funck, Mohammed Al-Kuwaiti, Claude Lepage, Peter Zepper, Jeffrey Minuk, Hyman M Schipper, Alan C Evans, Alexander Thiel
The peri-infarct cortex (PIC) is the site of long-term physiologic changes after ischemic stroke. Traditional methods for delineating the peri-infarct gray matter (GM) have used a volumetric Euclidean distance metric to define its extent around the infarct. This metric has limitations in the case of cortical stroke, i.e., those where ischemia leads to infarction in the cortical GM, because the vascularization of the cerebral cortex follows the complex, folded topology of the cortical surface. Instead, we used a geodesic distance metric along the cortical surface to subdivide the PIC into equidistant rings emanating from the infarct border and compared this new approach to a Euclidean distance metric definition...
September 10, 2016: Human Brain Mapping
Hyejin Yang, Junsung Woo, Ae Nim Pae, Min Young Um, Nam-Chul Cho, Ki Duk Park, Minseok Yoon, Jiyoung Kim, C Justin Lee, Suengmok Cho
α-Pinene is a major monoterpene of the pine tree essential oils. It has been reported that α-pinene shows anxiolytic and hypnotic effects upon inhaled administration. However, hypnotic effect by oral supplementation and the molecular mechanism of α-pinene have not been determined yet. By combining in vivo sleep behavior, ex vivo electrophysiological recording from brain slices, and in silico molecular modeling, we demonstrate that (-)-α-pinene shows sleep enhancing property through a direct binding to GABAA-benzodiazepine (BZD) receptors by acting as a partial modulator at the BZD binding site...
November 2016: Molecular Pharmacology
Lynn Marie Trotti, Prabhjyot Saini, Catherine Koola, Vincent LaBarbera, Donald L Bliwise, David B Rye
STUDY OBJECTIVES: Patients with central disorders of hypersomnolence sometimes do not achieve satisfactory symptom control with currently available wake-promoting medications. Based on the finding that the cerebrospinal fluid from some patients with hypersomnolence demonstrates potentiation of gamma-aminobutyric acid (GABA)-A receptors in excess of that of controls, a finding that reverses with flumazenil, we initiated prescribing compounded flumazenil to carefully selected, treatment-refractory hypersomnolent patients...
October 15, 2016: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
Amir Rashidian, Forogh Farhang, Habib Vahedi, Ahmad Reza Dehpour, Shahram Ejtemai Mehr, Saeed Mehrzadi, Seyed Mahdi Rezayat
BACKGROUND: Lippia citriodora Kunth is one of the Iranian traditional medicines for the treatment of convulsive disorders. The goal of this study is to investigate the anticonvulsant activity of the plant's leave ethanolic extract against electro- and chemoconvulsant-induced seizures in mice. METHODS: The anticonvulsant activity of the extract (200, 400, 800 mg/kg, per os, p.o.) was investigated in pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures in mice...
2016: International Journal of Preventive Medicine
Peter J H Scott, Xia Shao, Timothy J Desmond, Brian G Hockley, Phillip Sherman, Carole A Quesada, Kirk A Frey, Robert A Koeppe, Michael R Kilbourn, Nicolaas I Bohnen
Clarithromycin is a potential treatment for hypersomnia acting through proposed negative allosteric modulation of GABAA receptors. We were interested whether this therapeutic benefit might extend to Parkinson's disease (PD) patients because GABAergic neurotransmission is implicated in postural control. Prior to initiating clinical studies in PD patients, we wished to better understand clarithromycin's mechanism of action. In this work we investigated whether the proposed activity of clarithromycin at the GABAA receptor is associated with the benzodiazepine binding site using in vivo [(11)C]flumazenil positron emission tomography (PET) in primates and ex vivo [(3)H]flumazenil autoradiography in rat brain...
August 11, 2016: ACS Medicinal Chemistry Letters
Nobuaki Egashira, Hikari Iba, Haruna Kuwano, Rikako Kawanaka, Masaki Nagao, Hiroshi Moriyama, Takuya Watanabe, Kaori Kubota, Shutaro Katsurabayashi, Katsunori Iwasaki
In the present study, we investigated the effect of kamishoyosan (KSS) on conditioned fear-induced freezing in ovariectomized (OVX) rats. Socially isolated OVX rats showed the longest freezing time among the following four groups: group-housed sham-operated (Sham), isolated Sham, group-housed OVX, and isolated OVX rats. Repeated oral administration of KSS (30-300 mg/kg) reduced conditioned fear-induced freezing in socially isolated OVX rats. The reduction of freezing by KSS was reversed by flumazenil (3 mg/kg) and bicuculline (3 mg/kg)...
August 2016: Journal of Pharmacological Sciences
G S Taiwe, F C O Moto, S Pale, A K Kandeda, Amadou Dawe, N Kouemou, E R M Ayissi, G T Ngoupaye, J S K Njapdounke, G C N Nkantchoua, J P O Omam, D Pahaye, E Ngo Bum
Extracts of Feretia apodanthera Del. (Rubiaceae) have been extensively used in traditional Cameroonian medicine to treat a variety of diseases, including some neurological disorders. The present study was aimed to tests the anticonvulsant properties of the aqueous extract and the alkaloid fraction of the stem barks of Feretia apodanthera. The anticonvulsant investigation was carried out against bicuculline-, picrotoxin-, pentylenetetrazol-, Methyl-β-carboline-3-carboxylate-, N-Methyl-D-aspartate-, 4-aminopyridine-, and maximal electroshock-induced seizures or turning behavior in mice...
August 12, 2016: Epilepsy Research
Dennison Lim, Joe Melucci, Milisa K Rizer, Beth E Prier, Robert J Weber
PURPOSE: Implementation and refinement of an integrated electronic "trigger tool" for detecting adverse drug events (ADEs) is described. METHODS: A three-month prospective study was conducted at a large medical center to test and improve the positive predictive value (PPV) of an electronic health record-based tool for detecting ADEs associated with use of four "trigger drugs": the reversal agents flumazenil, naloxone, phytonadione, and protamine. On administration of a trigger drug to an adult patient, an electronic message was transmitted to two pharmacists, who reviewed cases in near real time (typically, on the same day) to detect actual or potential ADEs...
September 1, 2016: American Journal of Health-system Pharmacy: AJHP
Fatemeh Forouzanfar, Ahmad Ghorbani, Mahmoud Hosseini, Hassan Rakhshandeh
OBJECTIVE: Insomnia is accompanied by several health complications and the currently used soporific drugs can induce several side effects such as psychomotor impairment, amnesia, and tolerance. The present study was planned to investigate the sleep prolonging effect of Pinus eldarica. MATERIALS AND METHODS: Hydroalcoholic extract (HAE) of P. eldarica, its water fraction (WF), ethyl acetate fraction (EAF) and n-butanol fraction (NBF) were injected (intraperitoneally) to mice 30 min before administration of pentobarbital...
July 2016: Avicenna Journal of Phytomedicine
Allyson L Spence, Glenn F Guerin, Nicholas E Goeders
BACKGROUND: Methamphetamine is the second most commonly used illicit drug in the world, and despite recent attempts by the Drug Enforcement Administration to combat this epidemic, methamphetamine use is still on the rise. As methamphetamine use increases so does polydrug use, particularly that involving methamphetamine and benzodiazepines. The present study was designed to examine the effects of two benzodiazepines on methamphetamine self-administration. METHODS: Five doses of methamphetamine (0...
September 1, 2016: Drug and Alcohol Dependence
Inês R Violante, Miguel Patricio, Inês Bernardino, José Rebola, Antero J Abrunhosa, Nuno Ferreira, Miguel Castelo-Branco
OBJECTIVE: To provide a comprehensive investigation of the γ-aminobutyric acid (GABA) system in patients with neurofibromatosis type 1 (NF1) that allows understanding the nature of the GABA imbalance in humans at pre- and postsynaptic levels. METHODS: In this cross-sectional study, we employed multimodal imaging and spectroscopy measures to investigate GABA type A (GABAA) receptor binding, using [(11)C]-flumazenil PET, and GABA concentration, using magnetic resonance spectroscopy (MRS)...
August 30, 2016: Neurology
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