Search results for "benzodiazepine"
showing 10 items of 97 documents
GABAA receptors in the ventral tegmental area control the outcome of a social competition in rats
2018
Social dominance can be attained through social competitions. Recent work in both humans and rodents has identified trait anxiety as a crucial predictor of social competitiveness. In addition, the anxiolytic GABAA positive modulator, diazepam, injected either systemically or into the ventral tegmental area (VTA) was shown to increase social dominance. Here, we investigated the impact of pharmacologically targeting GABAA receptors in the VTA for the outcome of a social competition between two unfamiliar male rats, one of them infused with vehicle and the other one with the drug under study. We show that infusion of the GABAA receptor agonist, muscimol, reduced anxiety-like behaviors and enha…
GABAergic System in Action: Connection to Gastrointestinal Stress-related Disorders.
2017
Background: Currently, treatment of stress-related gastrointestinal disorders, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), is mainly symptomatic since there is no drug on the market that solves effectively diverse disease symptoms and comorbid states. Thus, recently GABA receptors have been identified within gastrointestinal system and it has been recognized that among various GABAergic drugs some of them influence gastrointestinal stress-related diseases. Firstly, benzodiazepines have been investigated due to their diverse effects: neuroimmunomodulatory, relief of visceral pain and anxiolytic action. Conclusion: The present review brings findings on the exp…
Development of novel 1,4-benzodiazepine-based Michael acceptors as antitrypanosomal agents
2016
Novel 1,4-benzodiazepines, endowed with a Michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. Among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against Trypanosoma brucei brucei (IC50 = 5.29 µM), coupled with a lack of cytotoxicity towards mammalian cells (TC50>100 µM).
Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model
2018
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. A reduction in neuronal inhibition mediated by γ-aminobutyric acid type A receptors (GABAARs) has been implicated in the pathophysiology of FXS. Neuroactive steroids (NASs) are known allosteric modulators of GABAAR channel function, but recent studies from our laboratory have revealed that NASs also exert persistent metabotropic effects on the efficacy of tonic inhibition by increasing the protein kinase C (PKC)-mediated phosphorylation of the α4 and β3 subunits which increase the membrane expression and boosts tonic inhibition. We have assessed the GABAergic signaling in the hippocampus of fragile X ment…
Autoradiographic imaging of altered synaptic αβγ2 and extrasynaptic αβ GABAA receptors in a genetic mouse model of anxiety
2004
Abstract To image the possible alterations in brain regional GABAA receptor subtype properties in a genetic animal model of human anxiety, mice heterozygous for the deletion of GABAA receptor γ2 subunit (γ2+/−) were studied using ligand autoradiographic assays on brain cryostat sections. The [ 35 S ]TBPS binding assay was designed to reveal impaired GABA and channel site coupling shown to be more prominent in recombinant α1/6β3 than in α1/2β3γ2 or β2 subunit-containing GABAA receptors expressed in HEK 293 cells. Increased GABA-insensitive [ 35 S ]TBPS binding in the γ2+/− mouse brains was evident in the cerebral cortex and in subcortical regions, the alterations being regionally similar to …
Intranasal midazolam for treating acute respiratory crises in a woman with stiff person syndrome.
2020
Stiff person syndrome (SPS) is a rare neurologic disorder characterized by progressively worsening rigidity and spasms of the axial and limb muscles. Dyspnea has been recently recognized as a common symptom in SPS,1 and life-threatening respiratory crises have been occasionally reported and suspected to be responsible for sudden death in these patients.2,3 The pathophysiologic mechanisms of these respiratory manifestations remain unclear. Some authors have hypothesized that rigidity and/or spasm of the muscles of the trunk could prevent normal rib cage movements and excursion of the diaphragm.1
Solid microcrystalline dispersion films as a new strategy to improve the dissolution rate of poorly water soluble drugs: A case study using olanzapine
2016
In this study, we evaluate the dissolution rate enhancement of solid microcrystalline dispersion (SMD) films of olanzapine (OLZ) formulated with four water-soluble polymers namely poly(N-vinylpyrrolidone) (PVP), poloxamer 188 (P188), poloxamer 407 (P407) and Soluplus(®) (SLP). Prepared formulations were characterised to determine particle size, morphology, hydrogen bonding interactions, thermal characteristics as well as in vitro dissolution studies conducted under sink conditions (pH 6.8). Particle size of OLZ in all formulations ranged between 42 and 58μm. Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR), Differential Scanning Calorimetry (DSC) and Hot-Stage…
Decreased benzodiazepine receptor binding in panic disorder measured by IOMAZENIL-SPECT. A preliminary report.
1994
Single photon emission tomography (SPECT) imaging of the central benzodiazepine receptor (BZr) became possible with the newly developed ligand 123I-IOMAZENIL. The BZr binding was investigated in ten patients with panic disorder (PP) compared to ten epileptic patients (EP). Panic patients had lower IOMAZENIL uptake rates in the frontal, occipital and temporal cortex than EP indicating the involvement of the BZr complex in panic disorder.
Altered benzodiazepine receptor sensitivity in alcoholism: a study with fMRI and acute lorazepam challenge.
2007
Previous studies suggested altered sensitivity of the GABA/benzodiazepine receptor system in alcoholic patients. Expanding on these findings, the present functional magnetic resonance imaging (fMRI) study aimed to assess whether a differential modulation of cognitive brain activation by an acute GABAergic drug challenge could be detected in patients with alcoholism. Eight detoxified male patients meeting DSM-IV criteria for alcohol dependence and nine healthy male control subjects were studied with fMRI while performing a 2-back working memory task. The fMRI scans were performed 1 h after intravenous administration of saline and again 1 h after 0.03 mg/kg lorazepam I.V. After saline, a task…
Separate and Combined Effects of a Benzodiazepine (Alprazolam) and Noise on Auditory Brainstem Responses in Man
1999
Auditory brainstem responses (ABRs) were recorded in 60 male or female, anxious or anxiety-free university students, before and after separated or simultaneous intake of alprazolam and exposure to noise. A significant increase of the latencies of the ABRs was found when subjects took alprazolam. This effect is consistent with the presence of gamma-aminobutyric acid (GABA), one of the neurotransmitters at terminals of cochlear efferent fibres A significant increase of the latencies was observed after noise alone. In subjects taking alprazolam when they are exposed to noise, the effect of noise on the ABR latencies is reduced, but not abolished. The effects of alprazolam on the ABR are consis…