keyword
MENU ▼
Read by QxMD icon Read
search

Gabaa receptor

keyword
https://www.readbyqxmd.com/read/29792150/synthesis-and-biological-evaluation-of-novel-2-3-disubstituted-benzofuran-analogues-of-gaba-as-neurotropic-agents
#1
Arturo Coaviche-Yoval, Hector Luna, Ricardo Tovar-Miranda, Marvin Antonio Soriano-Ursua, Jose G Trujillo-Ferrara
BACKGROUND: Benzofurans are heterocyclic compounds with neurotropic activity. Some have been developed for the treatment of acute and degenerative neuronal injuries. OBJECTIVE: To evaluate the in silico binding of some promising benzofurans on the GABA receptors, and the in vivo neurotropic activity of benzofuran analogues (BZF 6-10) of gamma-aminobutyric acid (GABA) on a seizure model. METHODS: The ligands with the best physicochemical attributes were docked on two GABA receptors (the alpha-1 subunit of GABAA-R and GBR1 subunit of GABAB-R)...
May 23, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29787738/altered-brain-activity-during-withdrawal-from-chronic-alcohol-is-associated-with-changes-in-il-6-signal-transduction-and-gabaergic-mechanisms-in-transgenic-mice-with-increased-astrocyte-expression-of-il-6
#2
Donna L Gruol, Salvador Huitron-Resendiz, Amanda J Roberts
Interleukin-6 (IL-6) is an important neuroimmune factor that is increased in the brain by alcohol exposure/withdrawal and is thought to play a role in the actions of alcohol on the brain. To gain insight into IL-6/alcohol/withdrawal interactions and how these interactions affect the brain, we are studying the effects of chronic binge alcohol exposure on transgenic mice that express elevated levels of IL-6 in the brain due to increased astrocyte expression (IL-6 tg) and their non-transgenic (non-tg) littermate controls...
May 19, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29787571/rnai-screening-of-subtracted-transcriptomes-reveals-tumor-suppression-by-taurine-activated-gabaa-receptors-involved-in-volume-regulation
#3
Camiel L C Wielders, Pim van Nierop, Tinke L Vormer, Floris Foijer, Joanne Verheij, Johannes C Lodder, Jesper B Andersen, Huibert D Mansvelder, Hein Te Riele
To identify coding and non-coding suppressor genes of anchorage-independent proliferation by efficient loss-of-function screening, we have developed a method for enzymatic production of low complexity shRNA libraries from subtracted transcriptomes. We produced and screened two LEGO (Low-complexity by Enrichment for Genes shut Off) shRNA libraries that were enriched for shRNA vectors targeting coding and non-coding polyadenylated transcripts that were reduced in transformed Mouse Embryonic Fibroblasts (MEFs)...
2018: PloS One
https://www.readbyqxmd.com/read/29787472/a-randomised-placebo-controlled-clinical-trial-with-the-%C3%AE-2-3-5-subunit-selective-gabaa-positive-allosteric-modulator-pf-06372865-in-patients-with-chronic-low-back-pain
#4
Rachel Gurrell, Pinky Dua, Gang Feng, Maria Sudworth, Mark Whitlock, David S Reynolds, Richard P Butt
The effect of PF-06372865, a subtype selective positive allosteric modulator (PAM) of the γ-aminobutyric acid type A (GABAA) receptor, on chronic low back pain was investigated in a randomised, placebo and active-controlled Phase 2 clinical trial. The parallel treatment group trial consisted of a 1 week single-blind placebo run in phase, followed by 4 weeks double-blind treatment. Patients were randomised to receive either PF-06372865, naproxen or placebo BID for 4 weeks. The primary endpoint was the numerical rating score (NRS) of low back pain intensity (LBPI) after 4 weeks of active treatment...
May 21, 2018: Pain
https://www.readbyqxmd.com/read/29785705/association-of-gabaa-receptor-gene-with-epilepsy-syndromes
#5
Musadiq Ahmad Bhat, Sameer Ahmad Guru, Rashid Mir, Ajaz Ahmad Waza, Mariyam Zuberi, Mamta Pervin Sumi, Shaam Bodeliwala, Vinod Puri, Alpana Saxena
GABA has always been an inviting target in the etiology and treatment of epilepsy. The GABRA1, GABRG2, and GABRD genes provide instructions for making α1, ϒ2, and δ subunits of GABAA receptor protein respectively. GABAA is considered as one of the most important proteins and has found to play an important role in many neurological disorders. We explored the association of GABAA receptor gene mutation/SNPs in JME and LGS patients in Indian population. A total of 100 epilepsy syndrome patients (50 JME and 50 LGS) and 100 healthy control subjects were recruited and analyzed by AS-PCR and RFLP-PCR techniques...
May 21, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29782207/the-benzodiazepine-anesthetic-midazolam-prevents-hyperglycemia-induced-microvascular-leakage-in-the-retinas-of-diabetic-mice
#6
Yeon-Ju Lee, Minsoo Kim, Jee-Yeon Lee, Se-Hui Jung, Hye-Yoon Jeon, Seung Ah Lee, Seongsik Kang, Eun-Taek Han, Won Sun Park, Seok-Ho Hong, Young-Myeong Kim, Kwon-Soo Ha
We investigated the beneficial effects of midazolam against vascular endothelial growth factor (VEGF)-induced vascular leakage and its molecular mechanism of action in human retinal endothelial cells (HRECs) and the retinas of diabetic mice. Midazolam inhibited VEGF-induced elevation of intracellular Ca2+ , generation of reactive oxygen species (ROS), and transglutaminase activation in HRECs; these effects were reversed by the GABA, type A (GABAA ) receptor antagonist flumazenil but not by the translocator protein antagonist PK11195...
May 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29781560/conditioned-reward-of-opioids-but-not-psychostimulants-is-impaired-in-gaba-a-receptor-%C3%AE-subunit-knockout-mice
#7
Milo S Siivonen, Elena de Miguel, Juho Aaltio, Aino K Manner, Mikko Vahermo, Jari Yli-Kauhaluoma, Anni-Maija Linden, Teemu Aitta-Aho, Esa R Korpi
Extrasynaptic δ subunit-containing γ-aminobutyric acid type A receptors (δ-GABAA Rs) are emerging as targets for a number of neuropsychopharmacological drugs, including the direct GABA-site agonist gaboxadol and neuroactive steroids. Among other regions, these δ-GABAA Rs are functionally expressed in the ventral tegmental area (VTA), the cell body region of mesocorticolimbic dopamine (DA) system important for motivated behaviors, and in the target region, the nucleus accumbens. Gaboxadol and neurosteroids induce VTA DA neuron plasticity ex vivo, by inhibiting the VTA GABA neurons, and aversive place conditioning, which are absent in the δ-GABAA R knockout mice (δ-KO)...
May 21, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29778948/bioisosteres-of-ethyl-8-ethynyl-6-pyridin-2-yl-4h-benzo-f-imidazo-1-5-a-1-4-diazepine-3-carboxylate-hz-166-as-novel-alpha-2-3-selective-potentiators-of-gaba-a-receptors-improved-bioavailability-enhances-anticonvulsant-efficacy
#8
J M Witkin, J L Smith, X Ping, S D Gleason, M M Poe, G Li, X Jin, J Hobbs, J M Schkeryantz, J S McDermott, A I Alatorre, J N Siemian, J W Cramer, D C Airey, K R Methuku, V V N P B Tiruveedhula, T M Jones, J Crawford, M J Krambis, J L Fisher, J M Cook, R Cerne
HZ-166 has previously been characterized as an α2,3-selective GABAA receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity...
May 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29775659/%C3%AE-2-receptors-in-the-lateral-parabrachial-nucleus-generates-the-pressor-response-of-the-cardiovascular-chemoreflex-effects-of-gaba-a-receptor
#9
Nafiseh Mirzaei Damabi, Gholam Reza Namvar, Fahimeh Yeganeh, Masoumeh Hatam
The lateral parabrachial nucleus (LPBN) is a pontine area involved in cardiovascular chemoreflex. This study was performed to find the effects of reversible synaptic blockade of the LPBN on the chemoreflex responses, and to find the roles of GABAA receptor and α2 -adenoreceptor (α2 -AR) in chemoreflex. It also aimed to seek possible interaction between GABA and noradrenergic systems of the LPBN in urethane-anesthetized male rats. Cardiovascular chemoreflex was activated by intravenous injection of potassium cyanide (KCN, 80 μg/kg)...
May 15, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29775570/rapid-non-classical-effects-of-steroids-on-the-membrane-receptor-dynamics-and-downstream-signaling-in-neurons
#10
REVIEW
Klaudia Barabás, Soma Godó, Ferenc Lengyel, Dávid Ernszt, József Pál, István M Ábrahám
Although rapid effects of steroid hormones on membrane receptors and intracellular signaling molecules have been extensively studied in neurons, we are only beginning to understand the molecular mechanisms behind these non-classical steroid actions. Single molecule tracking (SMT) studies on live cells demonstrated that surface trafficking of membrane receptors determines their ligand binding properties and downstream signaling events. Recent findings suggest that one of the underlying mechanisms of non-classical steroid actions is the alteration of receptor movements on the membrane surface...
May 15, 2018: Hormones and Behavior
https://www.readbyqxmd.com/read/29767950/different-benzodiazepines-bind-with-distinct-binding-modes-to-gaba-a-receptors
#11
Alshaimaa A Elgarf, David C B Siebert, Friederike Steudle, Angelika Draxler, Guanguan Li, Shengming Huang, James M Cook, Margot Ernst, Petra Scholze
Benzodiazepines are clinically relevant drugs, which bind to GABAA neurotransmitter receptors at the α+/γ2- interfaces and thereby enhance GABA induced chloride ion flux leading to neuronal hyperpolarization. However, the structural basis of benzodiazepine interactions with their high affinity site at GABAA receptors is controversially debated in the literature and in silico studies led to discrepant binding mode hypotheses. In the current study computational docking of diazepam into α+/γ2- homology models suggested that a chiral methyl group, which is known to promote preferred binding to α5-containing GABAA receptors (position 3 of the 7-membered diazepine ring), could possibly provide experimental evidence in favor of or against the so far proposed binding modes...
May 16, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29766792/gabaa-receptors-various-stoichiometrics-of-subunit-arrangement-in-%C3%AE-1%C3%AE-3-and-%C3%AE-1%C3%AE-3%C3%AE%C2%B5-receptors
#12
Ahmad Tarmizi Che Has, Mary Chebib
GABAA receptors (GABAARs) are members of the Cys-loop ligand-gated ion channel (LGIC) superfamily, which includes nicotinic acetylcholine, glycine, and serotonin (5HT3) receptors [1,2,3,4]. LGICs typically mediate fast synaptic transmission via the movement of ions through channels gated by neurotransmitters, such as acetylcholine for nicotinic receptors and GABA for GABAARs [5]. The term Cys-loop receptors originates from the presence of a conserved disulphide bond (or bridge) which holds together two cysteine amino acids of the loop that forms from the structure of polypeptides in the extracellular domain of the receptor's subunit [6]...
May 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29763637/neurosteroid-pregnenolone-sulfate-alone-and-as-augmentation-of-lurasidone-or-tandospirone-rescues-phencyclidine-induced-deficits-in-cognitive-function-and-social-interaction
#13
L Rajagopal, D Soni, H Y Meltzer
BACKGROUND: Pregnenolone sulfate (PregS), an endogenous neurosteroid, which negatively and positively modulates gamma amino butyric acid subunit A (GABAA ) and N-methyl D-aspartate (NMDA) receptors (R) respectively, among other potential neuroplastic changes on synaptic processes, has shown some beneficial effects on treating cognitive impairment associated with schizophrenia (CIAS) and negative symptoms. Lurasidone (Lur), an atypical antipsychotic drug (AAPD), and tandospirone (Tan), a 5-HT1A  R partial agonist, have also been reported to improve cognitive or negative symptoms, or both, in some schizophrenia patients...
May 12, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29758348/effect-of-prenatal-stress-on-%C3%A9-5-gaba-a-receptor-subunit-gene-expression-in-hippocampus-and-pilocarpine-induced-seizure-in-rats
#14
Mehrdad Nejatbakhsh, Ehsan Saboory, Morteza Bagheri
The GABAergic synapses go through structural and functional maturation during early brain development. Maternal stress alters GABAergic synapses in developing brain, which are associated with the pathophysiology of neuropsychiatric disorders in adults. The present study aimed to investigate the effect of prenatal restraint stress (PS) on pilocarpine-induced seizure and ɑ5 subunit of γ-amino butyric acid type A (GABAA ) receptor expression in hippocampus. Pregnant Wistar rats were subjected to PS at gestational days 15-17 and the pups were examined for susceptibility to seizure and ɑ5 subunit of GABAA receptor expression in hippocampus at postnatal days 14 and 21 (P14 and PND 21)...
May 11, 2018: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/29758302/plasminogen-binding-inhibitors-demonstrate-unwanted-activities-on-gaba-a-and-glycine-receptors-in-human-ipsc-derived-neurons
#15
Lisbeth Kristensson, Anders Lundin, David Gustafsson, Jan Fryklund, Tomas Fex, Delsing Louise, Erik Ryberg
Plasminogen binding inhibitors (PBIs) reduce the risk of bleeding in hemorrhagic conditions. However, generic PBIs are also associated with an increased risk of seizures, an adverse effect linked to unwanted activities towards inhibitory neuronal receptors. Development of novel PBIs serve to remove compounds with such properties, but progress is limited by a lack of higher throughput methods with human translatability. Herein we apply human induced pluripotent stem cell (hiPSC) derived neurons in combination with dynamic mass redistribution (DMR) technology to demonstrate robust and reproducible modulation of both GABAA and glycine receptors...
May 11, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29755316/single-ethanol-withdrawal-regulates-extrasynaptic-%C3%AE-gaba-a-receptors-via-pkc%C3%AE-activation
#16
Juan Chen, Yang He, Yan Wu, Hang Zhou, Li-Da Su, Wei-Nan Li, Richard W Olsen, Jing Liang, Yu-Dong Zhou, Yi Shen
Alcohol (ethanol, EtOH) is one of the most widely abused drugs with profound effects on brain function and behavior. GABAA receptors (GABAA Rs) are one of the major targets for EtOH in the brain. Temporary plastic changes in GABAA Rs after withdrawal from a single EtOH exposure occur both in vivo and in vitro , which may be the basis for chronic EtOH addiction, tolerance and withdrawal symptoms. Extrasynaptic δ-GABAA R endocytosis is implicated in EtOH-induced GABAA R plasticity, but the mechanisms by which the relative abundance and localization of specific GABAA Rs are altered by EtOH exposure and withdrawal remain unclear...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29750497/improved-synthesis-of-caged-glutamate-and-caging-each-functional-group
#17
Charitha Guruge, Yannick P Ouedraogo, Richard Louis Comitz, Jingxuan Ma, Attila Losonczy, Nasri Nesnas
Glutamate is an excitatory neurotransmitter that controls numerous pathways in the brain. Neuroscientists make use of photoremovable protecting groups, also known as cages, to release glutamate with precise spatial and temporal control. Various cage designs have been developed and amongst the most effective has been the nitroindolinyl caging of glutamate. We, hereby, report an improved synthesis of one of the current leading molecules of caged glutamate, 4-carboxymethoxy-5,7-dinitroindolinyl glutamate (CDNI-Glu), which possesses efficiencies with the highest reported quantum yield of at least 0...
May 11, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29746351/spinal-gabaa-receptors-for-pain-control-lost-in-translation
#18
Hanns Ulrich Zeilhofer, Elena Neumann, Gordon Munro
No abstract text is available yet for this article.
April 26, 2018: Pain
https://www.readbyqxmd.com/read/29744526/-drugs-for-intravenous-induction-of-anesthesia-barbiturates
#19
C Dumps, E Halbeck, D Bolkenius
The discovery of barbituric acid and research on its derivatives have long been of importance in advancements in modern anesthesia. Decades of clinical use of barbiturates worldwide and their abuse has led to an enormous amount of knowledge. Thiopental and methohexital are ultra-short acting derivatives of barbiturates. Their clinical application has been accompanied by an enormous increase in the knowledge of the pharmacology of cerebrally active drugs, in particular gamma-aminobutyric acid (GABAA ) receptor and GABA-induced effects on nerve cell membranes...
May 9, 2018: Der Anaesthesist
https://www.readbyqxmd.com/read/29743978/clarified-a%C3%A3-a%C3%A3-euterpe-oleracea-juice-as-an-anticonvulsant-agent-in-vitro-mechanistic-study-of-gabaergic-targets
#20
Gabriela P F Arrifano, Mathieu P Lichtenstein, José Rogério Souza-Monteiro, Marcelo Farina, Hervé Rogez, José Carlos Tavares Carvalho, Cristina Suñol, Maria Elena Crespo-López
Seizures affect about 50 million people around the world. Approximately 30% of seizures are refractory to the current pharmacological arsenal, so, the pursuit of new therapeutic alternatives is essential. Clarified Euterpe oleracea (EO) juice showed anticonvulsant properties similar to diazepam in an in vivo model with pentylenetetrazol, a GABAA receptor blocker. This study investigated the effects of EO on the main GABAergic targets for anticonvulsant drugs, analyzing the effect on the GABA receptor's benzodiazepine and picrotoxinin binding sites and the GABA uptake...
2018: Oxidative Medicine and Cellular Longevity
keyword
keyword
90913
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"