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GABA AND Oral

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https://www.readbyqxmd.com/read/29774754/effect-of-di-2-ethylhexyl-phthalate-on-the-neuroendocrine-regulation-of-reproduction-in-adult-male-rats-and-its-relationship-to-anxiogenic-behavior-participation-of-gabaergic-system
#1
S Carbone, O J Ponzo, N Gobetto, Y A Samaniego, R Reynoso, J A Moguilevsky, R A Cutrera
The endocrine disruptor di-(2-ethylhexyl) phthalate (DEHP) is used in a variety of consumer products made with polyvinyl chloride and also in the manufacture of medical devices. DEHP disrupts reproductive tract development in an antiandrogenic manner and also may induce neurobehavioral changes. The aim of this study was to investigate the effects of chronic postnatal exposure to DEHP (30 mg/kg body weight/day, orally from birth to day 60) on the neuroendocrine regulation of the gonadal axis and its impact on the anxiety-like behavior in adult male rats, as well as the probable participation of the GABAergic system in these effects...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29752742/j-difference-edited-mrs-measures-of-%C3%AE-aminobutyric-acid-before-and-after-acute-caffeine-administration
#2
Georg Oeltzschner, Helge J Zöllner, Marc Jonuscheit, Rotem S Lanzman, Alfons Schnitzler, Hans-Jörg Wittsack
PURPOSE: The aim of this study was to investigate potential effects of acute caffeine intake on J-difference-edited MRS measures of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA). METHODS: J-difference-edited Mescher-Garwood PRESS (MEGA-PRESS) and conventional PRESS data were acquired at 3T from voxels in the anterior cingulate and occipital area of the brain in 15 healthy subjects, before and after oral intake of a 200-mg caffeine dose. MEGA-PRESS data were analyzed with the MATLAB-based Gannet tool to estimate GABA+ macromolecule (GABA+) levels, while PRESS data were analyzed with LCModel to estimate levels of glutamate, glutamate+glutamine, N-acetylaspartate, and myo-inositol...
May 12, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29742655/gabapentin-for-the-treatment-of-vulvodynia-a-randomized-controlled-trial
#3
Candace S Brown, Gloria A Bachmann, Jim Wan, David C Foster
OBJECTIVE: To evaluate whether extended-release gabapentin is more effective than placebo among women with vulvodynia. METHODS: In a multicenter double-blind, placebo-controlled randomized crossover trial, gabapentin (1,200-3,000 mg/d) was compared with a placebo. The primary outcome was mean pain intensity (0, no pain at all to 10, worst pain ever) on the tampon test (a standardized tampon insertion and removal test used as a surrogate marker for dyspareunia) during the last 7 days of the maintenance phase...
May 7, 2018: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29720564/evidence-that-sedative-effects-of-benzodiazepines-involve-unexpected-gaba-a-receptor-subtypes-quantitative-observation-studies-in-rhesus-monkeys
#4
Angela N Duke, Zhiqiang Meng, Donna M Platt, John R Atack, Gerard R Dawson, David S Reynolds, V V N Phani Babu Tiruveedhula, Guanguan Li, Michael Rajesh Stephen, Werner Sieghart, James M Cook, James K Rowlett
Using non-human primates, we introduced a new set of behavioral categories for observable sedative effects based on pediatric anesthesiology classifications. We examined the effects of alprazolam and diazepam (non-selective benzodiazepines), zolpidem (preferential binding to α1 subunit-containing GABAA receptors), HZ-166 (8-ethynyl-6-(2'-pyridine)-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester; functionally selective for α2 and α3 subunit-containing GABAA receptors), MRK-696 (7-cyclobutyl-6-(2-methyl-2H-1,2,4-triazol-2-ylmethoxy)-3-(2-flurophenyl)-1,2,4-triazolo(4,3-b)pyridazine; no selectivity but partial intrinsic activity), and TPA023B (6,2'-difluro-5'-(3-(1-hydroxy-1-methylethyl)imidazo(1,2-b((1,2,4)triazin-7-yl)(1,1'-biphenyl)-2-carbonitrile; selectivity for α2, α3, α5 subunit-containing GABAA receptors) using quantitative behavioral observation techniques in rhesus monkeys...
May 2, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29710514/pathophysiological-investigations-anxiolytic-effects-and-interaction-of-a-semisynthetic-riparin-with-benzodiazepine-receptors
#5
Éverton José Ferreira de Araújo, Luís Mário Rezende-Júnior, Layana Karine Farias Lima, Marcelo Pereira da Silva-Júnior, Oskar Almeida Silva, Benedito Pereira de Sousa Neto, Antonia Amanda Cardoso de Almeida, Stanley Juan Chavez Gutierrez, Adriana da Rocha Tomé, Luciano da Silva Lopes, Paulo Michel Pinheiro Ferreira, Francisco das Chagas Alves Lima
We have reported Riparin A as a promising antiparasitic molecule ​​against Leishmania amazonensis promastigotes. This work evaluated the acute oral toxicity of Riparin A and its anxiolytic effects using in vivo models and computational tools. Mice were submitted to acute oral toxicity tests (Guideline OECD 423). Later, anxiety assays with Riparin A (50, 100 and 200 mg/kg: elevated plus maze, light/dark box and marble burying) were performed. Theoretical calculations analyzed interaction of Riparin A with gamma-amino butyric acid (GABA) receptors...
April 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29674331/ono-8590580-a-novel-gaba-a-%C3%AE-5-negative-allosteric-modulator-enhances-long-term-potentiation-and-improves-cognitive-deficits-in-preclinical-models
#6
Soichi Kawaharada, Miki Nakanishi, Nobuto Nakanishi, Keisuke Hazama, Masato Higashino, Arwel Lewis, Gary S Clark, Mark S Chambers, Scott A Maidment, Tetsuya Yasuhiro, Seishi Katsumata, Shuji Kaneko
GABAA receptors containing α5 subunits (GABAA α5) are highly expressed in the hippocampus and negatively involved in memory processing, as shown by the fact that GABAA α5 deficient mice show higher hippocampus-dependent performance than wild type mice. Accordingly, small molecule GABAA α5 negative allosteric modulators (NAMs) are known to enhance spatial learning and memory in rodents. Here we introduce a new, orally-available GABAA α5 NAM that improves hippocampal functions. ONO-8590580 binds to the benzodiazepine binding sites on recombinant human α5-containing GABAA receptors with a Ki of 7...
April 19, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29649764/sleep-after-intranasal-progesterone-vs-zolpidem-and-placebo-in-postmenopausal-women-a-randomized-double-blind-cross-over-study
#7
P Schüssler, M Kluge, M Adamczyk, M E Beitinger, P Beitinger, A Bleifuss, S Cordeiro, C Mattern, M Uhr, T C Wetter, A Yassouridis, R Rupprecht, E Friess, A Steiger
CONTEXT: The loss of progesterone during menopause is linked to sleep complaints of the affected women. Previously we demonstrated sleep promoting effects of oral progesterone replacement in postmenopausal women. The oral administration of progesterone, however, is compromised by individual differences in bioavailability and metabolism of the steroid. OBJECTIVE: We compared the sleep-endocrine effects after intranasal progesterone (MPP22), zolpidem and placebo in healthy postmenopausal women...
April 4, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29642911/gnrh-dysregulation-in-polycystic-ovarian-syndrome-pcos-is-a-manifestation-of-an-altered-neurotransmitter-profile
#8
Nirja Chaudhari, Mitali Dawalbhakta, Laxmipriya Nampoothiri
BACKGROUND: GnRH is the master molecule of reproduction that is influenced by several intrinsic and extrinsic factors such as neurotransmitters and neuropeptides. Any alteration in these regulatory loops may result in reproductive-endocrine dysfunction such as the polycystic ovarian syndrome (PCOS). Although low dopaminergic tone has been associated with PCOS, the role of neurotransmitters in PCOS remains unknown. The present study was therefore aimed at understanding the status of GnRH regulatory neurotransmitters to decipher the neuroendocrine pathology in PCOS...
April 11, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29621152/taurine-administration-recovers-motor-and-learning-deficits-in-an-angelman-syndrome-mouse-model
#9
Sara Guzzetti, Luciano Calzari, Lucia Buccarello, Valentina Cesari, Ivan Toschi, Stefania Cattaldo, Alessandro Mauro, Francesca Pregnolato, Silvia Michela Mazzola, Silvia Russo
Angelman syndrome (AS, MIM 105830) is a rare neurodevelopmental disorder affecting 1:10-20,000 children. Patients show moderate to severe intellectual disability, ataxia and absence of speech. Studies on both post-mortem AS human brains and mouse models revealed dysfunctions in the extra synaptic gamma-aminobutyric acid (GABA) receptors implicated in the pathogenesis. Taurine is a free intracellular sulfur-containing amino acid, abundant in brain, considered an inhibiting neurotransmitter with neuroprotective properties...
April 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29582256/probiotic-treatment-reduces-the-autistic-like-excitation-inhibition-imbalance-in-juvenile-hamsters-induced-by-orally-administered-propionic-acid-and-clindamycin
#10
Afaf El-Ansary, Abir Ben Bacha, Geir Bjørklund, Nora Al-Orf, Ramesa Shafi Bhat, Nadine Moubayed, Kawther Abed
Increasing evidence suggests that the gut microbiota plays a key role in the central nervous system (CNS), and alterations of the gut microbiota composition due to environmental factors can contribute to neurodevelopmental disorders. Animal modeling may help to identify drugs that can normalize the altered gut microbiota and thereby ameliorate abnormal brain signaling pathways. The purpose of the present study was to investigate the therapeutic potency of probiotics such as Bifidobacteria and Lactobacilli on glutamate excitotoxicity as a neurotoxic effect induced by clindamycin and propionic acid (PPA) in juvenile hamsters...
March 27, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29578347/a-novel-orally-available-asthma-drug-candidate-that-reduces-smooth-muscle-constriction-and-inflammation-by-targeting-gaba-a-receptors-in-the-lung
#11
Gloria S Forkuo, Amanda N Nieman, Revathi Kodali, Nicolas M Zahn, Guanguan Li, Shadiqur Rashid Roni, Michael Rajesh Stephen, Ted William Harris, Rajwana Jahan, Margaret L Guthrie, Olivia B Yu, Janet L Fisher, Gene T Yocum, Charles W Emala, Douglas A Steeber, Douglas C Stafford, James M Cook, Leggy A Arnold
We describe lead compound MIDD0301 for the oral treatment of asthma based on previously developed positive allosteric α5β3γ2 selective GABA(A) receptor (GABA(A)R) modulators. MIDD0301 relaxed airway smooth muscle at single micromolar concentrations as demonstrated with ex vivo guinea pig tracheal rings. MIDD0301 also attenuated airway hyperresponsiveness (AHR) in an ovalbumin murine model of asthma by oral administration. Reduced numbers of eosinophils and macrophages were observed in mouse broncho-alveolar lavage fluid without changing mucous metaplasia...
March 26, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29578001/long-term-administration-of-greek-royal-jelly-decreases-gaba-concentration-in-the-striatum-and-hypothalamus-of-naturally-aged-wistar-male-rats
#12
Justyna Pyrzanowska, Adriana Wawer, Ilona Joniec-Maciejak, Agnieszka Piechal, Kamilla Blecharz-Klin, Konstantia Graikou, Ioanna Chinou, Ewa Widy-Tyszkiewicz
Royal Jelly (RJ) is a unique substance obtained from bees that has been used widely in European and Asian traditional medicine for its potential to prevent signs of aging through its antioxidative, anti-inflammatory, anti-hyperglycemic and anti-hypercholesterolemic properties. We recently reported an enhancement in spatial memory along with changes in monoaminergic transmission in aged rats after chronic RJ administration. Here, we aim to further explore the action of RJ on central nervous system activity by examining levels of amino acids in selected brain structures of aged male Wistar rats following 2-months of Greek RJ administration...
March 22, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29492615/gr3027-reversal-of-neurosteroid-induced-gaba-a-receptor-mediated-inhibition-of-human-brain-function-an-allopregnanolone-challenge-study
#13
Maja Johansson, Maria Månsson, Lars-Eric Lins, Bruce Scharschmidt, Magnus Doverskog, Torbjörn Bäckström
RATIONALE: GR3027 is a novel small molecule GABA-A receptor-modulating steroid antagonist, which in non-clinical studies has shown promise for treatment of human disorders due to allosteric over-activation of GABA-A receptors by neurosteroids, such as allopregnanolone. We here studied its safety, pharmacokinetics, and ability to inhibit allopregnanolone effects in humans. METHODS: Safety and pharmacokinetics were studied in healthy adult males receiving ascending single or multiple oral GR3027 vs...
May 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29491273/antihypertensive-effect-of-%C3%AE-aminobutyric-acid-enriched-brown-rice-on-spontaneously-hypertensive-rats
#14
Kohei Kawakami, Kazuo Yamada, Takaya Yamada, Toru Nabika, Masato Nomura
'Haiibuki' is a giant embryo rice cultivar that contains abundant γ-aminobutyric acid (GABA) compared with conventional rice cultivars. Here, we performed a functional evaluation of 'GABA-enriched brown rice' (GEBR) prepared by modifying the 'Haiibuki' cultivar to contain more GABA. Study 1: Spontaneously hypertensive rats were divided into three groups [control (cornstarch), normal brown rice, and GEBR] and fed an orally administered diet for 4 wk. A significant blood pressure elevation-inhibitory effect was observed in the GEBR group as compared with the other groups...
2018: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/29460795/evidence-the-u-s-autism-epidemic-initiated-by-acetaminophen-tylenol-is-aggravated-by-oral-antibiotic-amoxicillin-clavulanate-augmentin-and-now-exponentially-by-herbicide-glyphosate-roundup
#15
Peter Good
Because certain hereditary diseases show autistic behavior, and autism often runs in families, researchers seek genes underlying the pathophysiology of autism, thus core behaviors. Other researchers argue environmental factors are decisive, citing compelling evidence of an autism epidemic in the United States beginning about 1980. Recognition that environmental factors influence gene expression led to synthesis of these views - an 'epigenetic epidemic' provoked by pervasive environmental agents altering expression of vulnerable genes, inducing characteristic autistic biochemistries in many mothers and infants...
February 2018: Clinical Nutrition ESPEN
https://www.readbyqxmd.com/read/29391360/gapp2-a-multicentre-randomised-controlled-trial-of-the-efficacy-of-gabapentin-for-the-management-of-chronic-pelvic-pain-in-women-study-protocol
#16
Katy Vincent, Andrew Baranowski, Siladitya Bhattacharya, Judy Birch, Ying Cheong, Roman Cregg, Jane Daniels, Catherine A Hewitt, Gary J Macfarlane, Lee Middleton, Wojciech Szubert, Irene Tracey, Amanda C de C Williams, Andrew W Horne
INTRODUCTION: Chronic pelvic pain (CPP) affects more than 1 million UK women with associated healthcare costs of £158 million annually. Current evidence supporting interventions when no underlying pathology is identified is very limited and treatment is frequently inadequate. Gabapentin (a GABA analogue) is efficacious and often well tolerated in other chronic pain conditions. We have completed a successful pilot randomised controlled trial Gabapentin for Pelvic Pain 1 (GaPP1) and here describe the protocol for our definitive multicentre trial to assess the efficacy of gabapentin in the management of CPP in women Gabapentin for Pelvic Pain 2 (GaPP2)...
January 31, 2018: BMJ Open
https://www.readbyqxmd.com/read/29390378/early-onset-epileptic-encephalopathy-with-a-novel-gabrb3-mutation-treated-effectively-with-clonazepam-a-case-report
#17
Yi Zhang, Yajun Lian, Nanchang Xie
RATIONALE: Early onset epileptic encephalopathy (EOEE) is one of the most serious early onset epilepsies. The etiopathology of this condition remains unclear, and recent evidence indicated that gamma-aminobutyric acid (GABA) A receptor, subunit beta 3 (GABRB3) gene mutations might be associated with EOEE. Furthermore, the therapeutic regimen for EOEE has yet to be well elucidated. Herein, we reported the clinical and genetic features of a case with GABRB3-related EOEE. PATIENT CONCERNS: A 6-year-old girl developed epileptic seizures 3 days after birth...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29372452/hibiscus-rosa-sinensis-mediate-anxiolytic-effect-via-modulation-of-ionotropic-gaba-a-receptors-possible-mechanism-of-action
#18
Zubia Begum, Ishrat Younus
The current study was designed with the aim to investigate anti-anxiety potential of Hibiscus rosa sinensis roots and its possible mechanism of action. For this purpose hole board test, elevated plus maze test and light/dark exploration test were employed. The ethanol extract of plant was administered orally at two different doses i.e. 100 and 500 mg/kg for consecutive 14 days. The results of present investigation indicate that plant extract significantly (p < 0.05) increased the number of head dips and rearings as compared to control on respective days of observation...
January 25, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29351468/gabaergic-contribution-to-the-muscle-mechanoreflex-mediated-heart-rate-responses-at-the-onset-of-exercise-in-humans
#19
André L Teixeira, Plinio S Ramos, Milena Samora, Jeann L Sabino-Carvalho, Djalma R Ricardo, Eduardo Colombari, Lauro C Vianna
Previous studies have indicated that central GABAergic mechanisms are involved in the heart rate (HR) responses at the onset of exercise. On the basis of previous research that showed similar increases in HR during passive and active cycling, we reasoned that the GABAergic mechanisms involved in the HR responses at the exercise onset are primarily mediated by muscle mechanoreceptor afferents. Therefore, in this study, we sought to determine whether central GABA mechanisms are involved in the muscle mechanoreflex-mediated HR responses at the onset of exercise in humans...
April 1, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29235903/brain-targeted-intranasal-zaleplon-solid-dispersion-in-hydrophilic-carrier-system-2-3-full-factorial-design-and-in-vivo-determination-of-gaba-neurotransmitter
#20
Eman Abd-Elrasheed, Sara Nageeb El-Helaly, Manal M El-Ashmoony, Salwa Salah
Intranasal zaleplon solid dispersion was formulated to enhance the solubility, bioavailability and deliver an effective therapy. Zaleplon belongs to Class II drugs, and undergoes extensive first-pass metabolism after oral absorption exhibiting 30% bioavailability. A 23 full-factorial design was chosen for the investigation of solid dispersion formulations. The effects of different variables include drug to carrier ratio (1:1 and 1:2), carrier type (polyethylene glycol 4000 and poloxamer 407), and preparation method (solvent evaporation and freeze drying) on different dissolution parameters were studied...
May 2018: Drug Development and Industrial Pharmacy
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