Read by QxMD icon Read

Gabaa inhibitor

Diego Dal Ben, Anna Marchenkova, Ajiroghene Thomas, Catia Lambertucci, Andrea Spinaci, Gabriella Marucci, Andrea Nistri, Rosaria Volpini
Blocking membrane currents evoked by the activation of purinergic P2X3 receptors localized on nociceptive neurons represents a promising strategy for the development of agents useful for the treatment of chronic pain conditions. Among compounds endowed with such antagonistic action, 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) is an ATP analogue, whose inhibitory activity on P2X receptors has been previously reported. Based on the results of molecular modelling studies performed with homology models of the P2X3 receptor, novel adenosine nucleotide analogues bearing cycloalkyl or arylalkyl substituents replacing the trinitrophenyl moiety of TNP-ATP were designed and synthesized...
October 18, 2016: Purinergic Signalling
Nicola Forte, Lucian Medrihan, Beatrice Cappetti, Pietro Baldelli, Fabio Benfenati
OBJECTIVE: The inhibition of glycolysis exerts potent antiseizure effects, as demonstrated by the efficacy of ketogenic and low-glucose/nonketogenic diets in the treatment of drug-resistant epilepsy. ATP-sensitive potassium (KATP ) channels have been initially identified as the main determinant of the reduction of neuronal hyperexcitability. However, a plethora of other mechanisms have been proposed. Herein, we report the ability of 2-deoxy-d-glucose (2-DG), a glucose analog that inhibits glycolytic enzymes, of potentiating γ-aminobutyric acid (GABA)ergic tonic inhibition via neurosteroid-mediated activation of extrasynaptic GABAA receptors...
October 13, 2016: Epilepsia
Amandine Dupuis, Anne-Sophie Wattiez, Jérémy Pinguet, Damien Richard, Frédéric Libert, Maryse Chalus, Youssef Aissouni, Benoit Sion, Denis Ardid, Philippe Marin, Alain Eschalier, Christine Courteix
Antidepressants are one of the first line treatments for neuropathic pain but their use is limited by the incidence and severity of side effects of tricyclics and the weak effectiveness of selective serotonin reuptake inhibitors (SSRIs). Serotonin type 2A (5-HT2A) receptors interact with PDZ proteins that regulate their functionality and SSRI efficacy to alleviate pain. We investigated whether an interfering peptide (TAT-2ASCV) disrupting the interaction between 5-HT2A receptors and associated PDZ proteins would improve the treatment of traumatic neuropathic allodynia...
September 20, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Emilia Grzęda, Eberhard Schlicker, Marek Toczek, Iwona Zalewska, Marta Baranowska-Kuczko, Barbara Malinowska
We have shown previously that the cannabinoid receptor agonist CP55940 microinjected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anaesthetized rats induces depressor and pressor cardiovascular effects in the absence and presence of the CB1 antagonist AM251, respectively. The aim of our study was to examine whether the hypotension and/or hypertension induced by CP55940 given into the PVN results from its influence on glutamatergic and GABAergic neurotransmission. CP55940 was microinjected into the PVN of urethane-anaesthetized rats twice (S1 and S2, 20 min apart)...
September 22, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Chia-Yuan Chang, Yi-Wen Chen, Tsu-Wei Wang, Wen-Sung Lai
Accumulating evidence implies that both AKT1 and GABAA receptor (GABAAR) subunit genes are involved in schizophrenia pathogenesis. Activated Akt promotes GABAergic neuron differentiation and increases GABAAR expression on the plasma membrane. To elucidate the role of Akt1 in modulating GABAergic functions and schizophrenia-related cognitive deficits, a set of 6 in vitro and in vivo experiments was conducted. First, an Akt1/2 inhibitor was applied to evaluate its effect on GABAergic neuron-like cell formation from P19 cells...
2016: Scientific Reports
Gabriela B L Spiacci, Leandro S Antero, Daniel G Reis, Sabrina F Lisboa, Leonardo B Resstel
The cannabinoid receptor type 1 (CB1) is highly expressed in the dorsal portion of hippocampus - a brain region that has been involved in the control of conditioned emotional response (CER) in the contextual fear conditioning (CFC) model. These responses are characterized by increased freezing behavior and autonomic parameters. Moreover, CB1 receptors activation negatively modulate the release of several neurotransmitters, including glutamate and GABA, which also have been related to modulation of CER. Therefore, our aim was to investigate the involvement of CB1 receptors in the dorsal hippocampus on CER expression...
October 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Keisuke Kakizawa, Miho Watanabe, Hiroki Mutoh, Yuta Okawa, Miho Yamashita, Yuchio Yanagawa, Keiichi Itoi, Takafumi Suda, Yutaka Oki, Atsuo Fukuda
Corticotropin-releasing hormone (CRH), which is synthesized in the paraventricular nucleus (PVN) of the hypothalamus, plays an important role in the endocrine stress response. The excitability of CRH neurons is regulated by γ-aminobutyric acid (GABA)-containing neurons projecting to the PVN. We investigated the role of GABA in the regulation of CRH release. The release of CRH was impaired, accumulating in the cell bodies of CRH neurons in heterozygous GAD67-GFP (green fluorescent protein) knock-in mice (GAD67(+/GFP)), which exhibited decreased GABA content...
August 2016: Science Advances
Gisele C Vaz, Neeru M Sharma, Hong Zheng, Matthew C Zimmerman, Robson S Santos, Frederic Frezard, Marco A P Fontes, Kaushik P Patel
BACKGROUND: Liposomes are concentric lipid vesicles that allow a sustained release of entrapped substances. GABA (γ-aminobutyric acid) is the most prevalent inhibitory neurotransmitter in the central nervous system. NEW METHOD: Using GABA-containing liposomes (GL) prepared by the freeze-thawing method, we determined the effect of sustained release of GABA on expression of neuronal nitric oxide synthase (nNOS) and GABAA receptor (GABAAR) in an in vitro neuronal model...
August 11, 2016: Journal of Neuroscience Methods
Licheng Chen, Hao Zheng, Shimeng Zhang
Epilepsy is a common type of neurological disorder with complex etiology. The mechanisms are still not clear. MicroRNAs are endogenous noncoding RNAs with many physiological activities. Multiple microRNAs were abnormally expressed in status epilepticus, including miR-210. In this study, we applied lithium chloride and pilocarpine to induce epileptic activity and aimed to disclose the potential mechanisms. Our data showed that miR-210 was significantly upregulated in hippocampus one day after modeling (P<0...
2016: Neuropsychiatric Disease and Treatment
Akshay Sridhar, Andrew J Johnston, Luxmmi Varathan, Sylvia E McLain, Philip C Biggin
Alprazolam is a benzodiazepine that is commonly prescribed for the treatment of anxiety and other related disorders. Like other benzodiazepines, it is thought to exert its effect through interaction with GABAA receptors. However, it has also been described as a potent and selective protein interaction inhibitor of bromodomain and extra-terminal (BET) proteins. Indeed, the only crystal structure of alprazolam bound to a protein is a complex between alprazolam and the BRD4 bromodomain. The structure shows that the complex also involves many water interactions that mediate contacts between the drug and the protein, a scenario that exists in many drug-protein complexes...
August 10, 2016: Physical Chemistry Chemical Physics: PCCP
Farzaneh Zolfagharian, Bibi Marjan Razavi, Hossein Hosseinzadeh
OBJECTIVE: Regarding the anticonvulsant effects of Satureja hortensis (S . hortensis) in Avicenna's book: canon of medicine; the present study was undertaken to evaluate the anti- eplileptic effects of S . hortensis aqueous and ethanolic aerial part extracts. Furthermore, the mechanisms of their anticonvulsant activities were also evaluated. MATERIALS AND METHODS: Seizure was induced by Pentylentetrazol (PTZ) and MES (maximal electroshock) models. Mice were randomly divided into 8 groups; negative control (normal saline, 10ml/Kg), positive control (diazepam, 2 mg/kg), S...
May 2016: Avicenna Journal of Phytomedicine
Renjun Wang, Wen Zhang, Zengxiang Dong, Yunfeng Qi, Michael Hultström, Xiaofu Zhou, En Yin Lai
AIM: Prostaglandin E2 mediates sympathoexcitation in chronic heart failure (CHF) through EP3 receptors (PTGER3) in the paraventricular nucleus (PVN). The aim of the present study was investigate the role of c-Jun N-terminal kinase (JNK) in expressional regulation of gamma-aminobutyric acid signaling in PVN of CHF rats. METHODS: CHF was induced by left coronary ligation in wistar rats. Renal sympathetic nerve activity and mean arterial pressure responses to the PVN infusion were determined in anesthetized rats...
July 20, 2016: Acta Physiologica
Yu-Hsiang Liao, Hsin-Jung Lee, Wei-Jan Huang, Pi-Chuan Fan, Lih-Chu Chiou
RATIONALE: Hispidulin is a flavonoid we isolated from Clerodendrum inerme, an herb that effectively remitted a case of intractable motor tic disorders. Hispidulin was shown to be a positive allosteric modulator (PAM) of GABAA receptors, including the α6 subunit-containing subtype (α6GABAAR) that is predominantly expressed in cerebellar granule cells and insensitive to diazepam. OBJECTIVES: We explored the action mechanism(s) of hispidulin using hyperdopaminergic mouse models induced by methamphetamine and apomorphine, based on the hyperdopaminergic nature of tic disorders...
September 2016: Psychopharmacology
R Hama, C L Bennett
Oseltamivir is contraindicated for people aged 10-19 in principle in Japan, due to concern about abnormal behaviours. Sudden death is another concern. This review examines growing evidence of their association and discusses underlying mechanisms of these sudden-onset type reactions to oseltamivir. First, the importance of animal models and the concept of human equivalent dose (HED) is summarized. Second, the specific condition for oseltamivir use, influenza infection, is reviewed. Third, findings from toxicity studies conducted prior to and after the marketing of oseltamivir are reported on to provide context on the observation of a possible causal association...
June 30, 2016: Acta Neurologica Scandinavica
Lionel Budry, Khalil Bouyakdan, Stephanie Tobin, Demetra Rodaros, Ann-Britt Marcher, Susanne Mandrup, Stephanie Fulton, Thierry Alquier
Diazepam is well known for its anxiolytic properties, which are mediated via activation of the GABAA receptor. Diazepam Binding Inhibitor (DBI), also called acyl-CoA binding protein (ACBP), is a ubiquitously expressed protein originally identified based on its ability to displace diazepam from its binding site on the GABAA receptor. Central administration of ACBP or its cleaved fragment, commonly referred to as endozepines, induces proconflict and anxiety-like behaviour in rodents. For this reason, ACBP is known as an anxiogenic peptide...
October 15, 2016: Behavioural Brain Research
Oliver Jonas, David Calligaris, Kashi Reddy Methuku, Michael M Poe, Jessica Pierre Francois, Frank Tranghese, Armen Changelian, Werner Sieghart, Margot Ernst, Daniel A Pomeranz Krummel, James M Cook, Scott L Pomeroy, Michael Cima, Nathalie Y R Agar, Robert Langer, Soma Sengupta
Medulloblastoma is the most common childhood malignant brain tumor. The most lethal medulloblastoma subtype exhibits a high expression of the GABAA receptor α5 subunit gene and MYC amplification. New benzodiazepines have been synthesized to function as α5-GABAA receptor ligands. To compare their efficacy with that of standard-of-care treatments, we have employed a newly developed microscale implantable device that allows for high-throughput localized intratumor drug delivery and efficacy testing. Microdoses of each drug were delivered into small distinct regions of tumors, as confirmed by tissue mass spectrometry, and the local drug effect was determined by immunohistochemistry...
June 2016: Journal of Biomedical Nanotechnology
Yan Sun, Jonathan O Lipton, Lara M Boyle, Joseph R Madsen, Marti C Goldenberg, Alvaro Pascual-Leone, Mustafa Sahin, Alexander Rotenberg
OBJECTIVE: To obtain insights into mechanisms mediating changes in cortical excitability induced by cathodal transcranial direct current stimulation (tDCS). METHODS: Neocortical slices were exposed to direct current stimulation (DCS) delivered through Ag/AgCl electrodes over a range of current orientations, magnitudes, and durations. DCS-induced cortical plasticity and its receptor dependency were measured as the change in layer II/III field excitatory postsynaptic potentials by a multielectrode array, both with and without neurotransmitter receptor blockers or allosteric modulators...
August 2016: Annals of Neurology
Zhiqiang Meng, James K Rowlett
BACKGROUND: Progesterone-derived neuroactive steroids have shown promise clinically (e.g., anti-seizure medications) but, as with other GABAA receptor modulators (e.g., benzodiazepines), may have the potential for abuse. METHODS: We evaluated the reinforcing effects of progesterone, a steroid precursor of endogenous neuroactive steroids, with and without pretreatments with the neuroactive steroid synthesis inhibitor, finasteride, in rhesus monkeys trained under a progressive-ratio (PR) schedule of i...
August 1, 2016: Drug and Alcohol Dependence
Ana Flávia Seraine Custódio Viana, Francilene Vieira da Silva, Hélio de Barros Fernandes, Irisdalva Sousa Oliveira, Milena Aguiar Braga, Paulo Iury Gomes Nunes, Daniel de Araújo Viana, Damião Pergentino de Sousa, Vietla Satyanarayana Rao, Rita de Cássia Meneses Oliveira, Flávia Almeida Santos
OBJECTIVES: (-)-Myrtenol is a natural fragrance monoterpenoid structurally related to α-pinene found in diverse plant essential oils. This study was aimed to assess the anti-ulcerogenic potential of (-)-myrtenol against ethanol-induced gastric lesions and to elucidate the underlying mechanism(s). METHODS: Gastroprotective activity of (-)-myrtenol was evaluated using the mouse model of ethanol-induced gastric damage. To elucidate the gastroprotective mechanism(s), the roles of GABA, prostaglandins, nitric oxide and KATP channels were assessed...
August 2016: Journal of Pharmacy and Pharmacology
Claudiu T Supuran
INTRODUCTION: Neuropathic pain affects up to 8% of the population with few therapeutic options for its management. No specific drugs are approved for its treatment. AREAS COVERED: Recent advances in understanding the pathological mechanisms of this syndrome and the biochemical/pharmacological characterization of novel drug targets, evidenced carbonic anhydrase (CA, EC inhibition as a new approach for designing antineuropathic pain agents. Expert commentary: Peripheral nerve injury negatively influences spinal γ-aminobutyric (GABA)-ergic networks via a reduction in the neuron-specific potassium-chloride (K(+)-Cl(-)) cotransporter (KCC2), which leads to neuropathic allodynia...
August 2016: Expert Review of Neurotherapeutics
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"