keyword
MENU ▼
Read by QxMD icon Read
search

Bumetanide autism

keyword
https://www.readbyqxmd.com/read/28818303/nkcc1-chloride-importer-antagonists-attenuate-many-neurological-and-psychiatric-disorders
#1
REVIEW
Yehezkel Ben-Ari
In physiological conditions, adult neurons have low intracellular Cl(-) [(Cl(-))I] levels underlying the γ-aminobutyric acid (GABA)ergic inhibitory drive. In contrast, neurons have high (Cl(-))I levels and excitatory GABA actions in a wide range of pathological conditions including spinal cord lesions, chronic pain, brain trauma, cerebrovascular infarcts, autism, Rett and Down syndrome, various types of epilepsies, and other genetic or environmental insults. The diuretic highly specific NKCC1 chloride importer antagonist bumetanide (PubChem CID: 2461) efficiently restores low (Cl(-))I levels and attenuates many disorders in experimental conditions and in some clinical trials...
August 14, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28485727/effects-of-bumetanide-on-neurobehavioral-function-in-children-and-adolescents-with-autism-spectrum-disorders
#2
E Lemonnier, N Villeneuve, S Sonie, S Serret, A Rosier, M Roue, P Brosset, M Viellard, D Bernoux, S Rondeau, S Thummler, D Ravel, Y Ben-Ari
No abstract text is available yet for this article.
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28291262/effects-of-bumetanide-on-neurobehavioral-function-in-children-and-adolescents-with-autism-spectrum-disorders
#3
E Lemonnier, N Villeneuve, S Sonie, S Serret, A Rosier, M Roue, P Brosset, M Viellard, D Bernoux, S Rondeau, S Thummler, D Ravel, Y Ben-Ari
In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl(-))i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3-11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I)...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28192112/multiple-blood-brain-barrier-transport-mechanisms-limit-bumetanide-accumulation-and-therapeutic-potential-in-the-mammalian-brain
#4
Kerstin Römermann, Maren Fedrowitz, Philip Hampel, Edith Kaczmarek, Kathrin Töllner, Thomas Erker, Douglas H Sweet, Wolfgang Löscher
There is accumulating evidence that bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-Cl cotransporter isoform NKCC1. However, following systemic administration, brain levels of bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders...
February 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28110691/is-insulin-growth-factor-1-the-future-for-treating-autism-spectrum-disorder-and-or-schizophrenia
#5
Rami Bou Khalil
To date, no curative psychopharmacologic treatment exists for the core symptoms of autism spectrum disorder (ASD) as well as for schizophrenia. Bumatenide is a specific antagonist of the first isoform of the Na-K-Cl cotransporter (NKCC1). It is usually used as a diuretic but may also promote a decrease in intraneuronal chloride ion concentration leading to hyperpolarization in neuronal membrane and subsequent decrease in neuronal hyperexcitability. This physiologic effect has been considered to be behind the relative efficacy of bumetanide in improving symptoms of ASD and, to a lesser extent, schizophrenia...
February 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/27147965/failure-of-the-nemo-trial-bumetanide-is-a-promising-agent-to-treat-many-brain-disorders-but-not-newborn-seizures
#6
Yehezkel Ben-Ari, Philippe Damier, Eric Lemonnier
The diuretic bumetanide failed to treat acute seizures due to hypoxic ischemic encephalopathy (HIE) in newborn babies and was associated with hearing loss (NEMO trial, Pressler et al., 2015). On the other hand, clinical and experimental observations suggest that the diuretic might provide novel therapy for many brain disorders including Autism Spectrum Disorders (ASD), schizophrenia, Rett syndrome, and Parkinson disease. Here, we discuss the differences between the pathophysiology of severe recurrent seizures in the neonates and neurological and psychiatric disorders stressing the uniqueness of severe seizures in newborn in comparison to other disorders...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/26966887/treating-schizophrenia-with-the-diuretic-bumetanide-a-case-report
#7
Eric Lemonnier, Alain Lazartigues, Yehezkel Ben-Ari
Administration of the diuretic and NKCC1 chloride cotransporter antagonist bumetanide reduces the severity of autism spectrum disorders in children, and this effect is mediated by a reduction of the elevated intracellular chloride concentrations and a reinforcement of GABAergic inhibition (Lemonnier et al Transl Psychiatry. 2012;2:e202; Tyzio et al Science. 2014;343:675-679). Here, we report that this treatment also reduces the severity of symptoms in an adolescent with schizophrenia. Long-term treatment reduced hallucinations significantly, suggesting that this treatment may also be useful to treat schizophrenia...
March 2016: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/26411965/expanding-spectrum-of-sodium-potassium-chloride-co-transporters-in-the-pathophysiology-of-diseases
#8
REVIEW
Amteshwar Singh Jaggi, Aalamjeet Kaur, Anjana Bali, Nirmal Singh
Sodium potassium chloride co-transporter (NKCC) belongs to cation-dependent chloride co-transporter family, whose activation allows the entry of Na(+), K(+) and 2Cl(-) inside the cell. It acts in concert with K(+) Cl(-) co-transporter (KCC), which extrudes K(+) and Cl(-) ions from cell. NKCC1 is widely distributed throughout the body, while NKCC2 is exclusively present in kidney. Protein kinase A, protein kinase C, Ste20-related proline-alanine-rich kinase, oxidative stress responsive kinases, With No K=lysine kinase and protein phosphatase type 1 control the phosphorylation/dephosphorylation of key threonine residues of in regulatory domain of NKCC1...
2015: Current Neuropharmacology
https://www.readbyqxmd.com/read/26287360/-research-advances-in-the-management-of-autism-spectrum-disorders-in-children
#9
REVIEW
Hong-Hua Li, Ling Shan, Lin Du, Fei-Yong Jia
Autism spectrum disorders (ASD) are a group of developmental dysfuntion of nervous system characterized by social interaction and communication disorders, restricted interests and repetitive stereotyped behaviors. The incidence of ASD has been increasing through the world. Some studies have shown that early reasonable individualized comprehensive intervention can obviously improve the prognosis of children with ASD. The etiology of ASD is unclear now, and behavioral and developmental intervention is the main therapy for ASD...
August 2015: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/26258842/a-pilot-study-on-the-combination-of-applied-behavior-analysis-and-bumetanide-treatment-for-children-with-autism
#10
RANDOMIZED CONTROLLED TRIAL
Lin Du, Ling Shan, Bing Wang, Honghua Li, Zhida Xu, Wouter G Staal, Feiyong Jia
OBJECTIVE: The purpose of this study was to investigate the therapeutic effects of combined bumetanide and applied behavior analysis (ABA) treatment in children with autism. METHODS: Sixty children diagnosed with autism according to the International Classification of Diseases, Tenth Revision (ICD-10) criteria (mean age of 4.5 years) were randomly divided into two groups: A single treatment group (n=28) and a combined treatment group (n=32). The combined treatment group received ABA training combined with oral bumetanide (0...
September 2015: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/26216321/paradoxical-benzodiazepine-response-a-rationale-for-bumetanide-in-neurodevelopmental-disorders
#11
Hilgo Bruining, Laurien Passtoors, Natalia Goriounova, Floor Jansen, Britt Hakvoort, Maretha de Jonge, Simon-Shlomo Poil
The diuretic agent bumetanide has recently been put forward as a novel, promising treatment of behavioral symptoms in autism spectrum disorder (ASD) and related conditions. Bumetanide can decrease neuronal chloride concentrations and may thereby reinstate γ-aminobutyric acid (GABA)-ergic inhibition in patients with neurodevelopmental disorders. However, strategies to select appropriate candidates for bumetanide treatment are lacking. We hypothesized that a paradoxical response to GABA-enforcing agents such as benzodiazepines may predict the efficacy of bumetanide treatment in neurodevelopmental disorders...
August 2015: Pediatrics
https://www.readbyqxmd.com/read/25766676/alterations-in-sociability-and-functional-brain-connectivity-caused-by-early-life-seizures-are-prevented-by-bumetanide
#12
Gregory L Holmes, Chengju Tian, Amanda E Hernan, Sean Flynn, Devon Camp, Jeremy Barry
There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype...
May 2015: Neurobiology of Disease
https://www.readbyqxmd.com/read/25490899/the-effect-of-organic-anion-transporter-3-inhibitor-probenecid-on-bumetanide-levels-in-the-brain-an-integrated-in-vivo-microdialysis-study-in-the-rat
#13
Maria D Donovan, Fionn E O'Brien, Geraldine B Boylan, John F Cryan, Brendan T Griffin
OBJECTIVES: Recent data highlight the potential of bumetanide as a treatment for neonatal seizures and autism, as it facilitates the excitatory to inhibitory switch in gamma-aminobutyric acid signalling. This study examines the extent of blood-brain barrier (BBB) permeation of bumetanide, a key determinant of the efficacy of centrally acting drugs. Furthermore, the impact of efflux transporter organic anion transporter 3 (oat3) inhibition on bumetanide pharmacokinetics was investigated...
April 2015: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/25449033/the-organic-anion-transport-inhibitor-probenecid-increases-brain-concentrations-of-the-nkcc1-inhibitor-bumetanide
#14
Kathrin Töllner, Claudia Brandt, Kerstin Römermann, Wolfgang Löscher
Bumetanide is increasingly being used for experimental treatment of brain disorders, including neonatal seizures, epilepsy, and autism, because the neuronal Na-K-Cl cotransporter NKCC1, which is inhibited by bumetanide, is implicated in the pathophysiology of such disorders. However, use of bumetanide for treatment of brain disorders is associated with problems, including poor brain penetration and systemic adverse effects such as diuresis, hypokalemic alkalosis, and hearing loss. The poor brain penetration is thought to be related to its high ionization rate and plasma protein binding, which restrict brain entry by passive diffusion, but more recently brain efflux transporters have been involved, too...
January 5, 2015: European Journal of Pharmacology
https://www.readbyqxmd.com/read/25301611/response-to-comment-on-oxytocin-mediated-gaba-inhibition-during-delivery-attenuates-autism-pathogenesis-in-rodent-offspring
#15
COMMENT
Sanaz Eftekhari, Amene Shahrokhi, Vera Tsintsadze, Romain Nardou, Corinne Brouchoud, Magali Conesa, Nail Burnashev, Diana C Ferrari, Yehezkel Ben-Ari
Bambini-Junior et al. questioned whether our treatment in two rodent models of autism has a long-lasting effect into adulthood. In response, we show that bumetanide treatment around delivery attenuates autistic behavioral features in adult offspring. Therefore, the polarity of γ-aminobutyric acid (GABA) actions during delivery exerts long-lasting priming actions after birth.
October 10, 2014: Science
https://www.readbyqxmd.com/read/25301610/comment-on-oxytocin-mediated-gaba-inhibition-during-delivery-attenuates-autism-pathogenesis-in-rodent-offspring
#16
COMMENT
Victorio Bambini-Junior, Gustavo Della Flora Nunes, Tomasz Schneider, Carmem Gottfried
Tyzio et al. (Reports, 7 February 2014, p. 675) reported that bumetanide restored the impaired oxytocin-mediated γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery in animal models of autism, ameliorating some autistic-like characteristics in the offspring. However, standard practices in the study of these models, such as the use of sex-dimorphic or males-only analyses and implementation of tests measuring social behavior, are lacking to definitely associate their findings to autism.
October 10, 2014: Science
https://www.readbyqxmd.com/read/25072038/gabaergic-signaling-as-therapeutic-target-for-autism-spectrum-disorders
#17
REVIEW
Giada Cellot, Enrico Cherubini
γ-Aminobutyric acid (GABA), the main inhibitory neurotransmitter in the adult brain, early in postnatal life exerts a depolarizing and excitatory action. This depends on accumulation of chloride inside the cell via the cation-chloride importer NKCC1, being the expression of the chloride exporter KCC2 very low at birth. The developmentally regulated expression of KCC2 results in extrusion of chloride with age and a shift of GABA from the depolarizing to the hyperpolarizing direction. The depolarizing action of GABA leads to intracellular calcium rise through voltage-dependent calcium channels and/or N-methyl-d-aspartate receptors...
2014: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/24503856/oxytocin-mediated-gaba-inhibition-during-delivery-attenuates-autism-pathogenesis-in-rodent-offspring
#18
Roman Tyzio, Romain Nardou, Diana C Ferrari, Timur Tsintsadze, Amene Shahrokhi, Sanaz Eftekhari, Ilgam Khalilov, Vera Tsintsadze, Corinne Brouchoud, Genevieve Chazal, Eric Lemonnier, Natalia Lozovaya, Nail Burnashev, Yehezkel Ben-Ari
We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes...
February 7, 2014: Science
https://www.readbyqxmd.com/read/24488662/the-effect-of-bumetanide-treatment-on-the-sensory-behaviours-of-a-young-girl-with-asperger-syndrome
#19
Marine Grandgeorge, Eric Lemonnier, Céline Degrez, Nelle Jallot
Sensory behaviours were not considered as core features of autism spectrum disorders until recently. However, they constitute an important part of the observed symptoms that result in social maladjustment and are currently quite difficult to treat. One promising strategy for the treatment of these behaviours is the use of bumetanide, which was previously shown to reduce the severity of autism spectrum disorders. In this study, we proposed to evaluate sensory behaviours using Dunn's Sensory Profile after 18 months of bumetanide treatment in a 10-year-old girl with Asperger syndrome...
2014: BMJ Case Reports
https://www.readbyqxmd.com/read/24343334/improving-emotional-face-perception-in-autism-with-diuretic-bumetanide-a-proof-of-concept-behavioral-and-functional-brain-imaging-pilot-study
#20
Nouchine Hadjikhani, Nicole R Zürcher, Ophelie Rogier, Torsten Ruest, Loyse Hippolyte, Yehezkel Ben-Ari, Eric Lemonnier
Clinical observations have shown that GABA-acting benzodiazepines exert paradoxical excitatory effects in autism, suggesting elevated intracellular chloride (Cl-)i and excitatory action of GABA. In a previous double-blind randomized study, we have shown that the diuretic NKCC1 chloride importer antagonist bumetanide, that decreases (Cl-)i and reinforces GABAergic inhibition, reduces the severity of autism symptoms. Here, we report results from an open-label trial pilot study in which we used functional magnetic resonance imaging and neuropsychological testing to determine the effects of 10 months bumetanide treatment in adolescents and young adults with autism...
February 2015: Autism: the International Journal of Research and Practice
keyword
keyword
77112
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"