Search results for "Benzodiazepine"
showing 10 items of 97 documents
Characterization of the muscarinic receptor subtype(s) mediating contraction of the guinea-pig lung strip and inhibition of acetylcholine release in …
1997
1 The muscarinic receptor subtypes mediating contraction of the guinea-pig lung strip and inhibition of the release of acetylcholine from cholinergic vagus nerve endings in the guinea-pig trachea in vitro have previously been characterized as M-2-like, i.e. having antagonist affinity profiles that are qualitatively similar but quantitatively dissimilar compared to cardiac M-2 receptors. The present study sought to establish definitely the identity of these receptor subtypes by using the selective muscarinic receptor antagonist, tripitramine. Guinea-pig atria and guinea-pig trachea (postjunctional contractile response) were included for reference.2 It was found that tripitramine antagonized …
Use of prescription benzodiazepines and related drugs in family caregivers: a nation-wide register-based study
2022
Abstract Background objective indicators of sleep and mental health problems in family caregivers have rarely been reported. Objective to study the use of prescription benzodiazepines and related drugs (BZDRD) in Finnish family caregivers and matched controls. Design prospective follow-up in 2012–17. Setting nationwide register-linkage study. Subjects all individuals who received family caregiver’s allowance in Finland in 2012 (N = 42,256; mean age 67 years; 71% women) and controls matched for age, sex and municipality of residence (N = 83,618). Methods information on purchases of prescription BZDRD, including the number of defined daily doses (DDDs), between 2012 and 2017 was obtained from…
Organotypic rat cerebellar slice culture as a model to analyze the molecular pharmacology of GABAA receptors
2002
The preservation of the neuronal circuitry in rat cerebellar slice cultures provides an advantage in monitoring the development and characterizing the pharmacology of GABA(A) receptor subtypes. Sprague-Dawley rats, 8-11 days of age, were decapitated, their cerebella were cut into 400-microm slices and transferred into culture dishes. Cell viability and organotypic cerebellar organization of the culture remained well preserved up to 3 weeks. Autoradiographic procedures were introduced in these advanced culture technique and employed [(3)H]Ro 15-4513 in the absence and presence of 10 microM diazepam to visualize all benzodiazepine (BZD) and diazepam-insensitive (DIS) binding sites, respective…
Characterization of γ-aminobutyrate type A receptors with atypical coupling between agonist and convulsant binding sites in discrete brain regions
2001
Abstract γ-Aminobutyric acid type A (GABA A ) receptor ionophore ligand t -[ 35 S]butylbicyclophosphorothionate ([ 35 S]TBPS) was used in an autoradiographic assay on brain cryostat sections to visualize and characterize atypical GABA-insensitive [ 35 S]TBPS binding previously described in certain recombinant GABA A receptors and the cerebellar granule cell layer. Picrotoxinin-sensitive but 1-mM GABA-insensitive [ 35 S]TBPS binding was present in the rat cerebellar granule cell layer, many thalamic nuclei, subiculum and the internal rim of the cerebral cortex, amounting in these regions up to 6% of the basal binding determined in the absence of exogenous GABA. Similar binding properties wer…
Behavioral Effects of GABAA Receptor Stimulation and GABA-Transporter Inhibition
2000
Abstract The present analysis addressed behavioral changes after treatment with 4.5 mg/kg or 18.5 mg/kg of the GABA-uptake inhibitor tiagabine combined with either the benzodiazepine diazepam (1.5 mg/kg) or the imidazopyridine zolpidem (0.05 mg/kg), the latter two acting differentially on GABA A receptor subtypes. The study included 97 male PVG/OIaHsd rats. A standard open field, an enriched open field, and an elevated plus-maze was used to study rat behavior. Treatment with the low dose of tiagabine alone induced no specific behavioral effects, whereas the high dose had an anxiolytic-like potential. Furthermore, diazepam but not zolpidem displayed anxiolytic-like effects. Combination of ea…
Altered receptor subtypes in the forebrain of GABAA receptor δ subunit-deficient mice: recruitment of γ2 subunits
2002
A GABA(A) receptor delta subunit-deficient mouse line was created by homologous recombination in embryonic stem cells to investigate the role of the subunit in the brain GABA(A) receptors. High-affinity [(3)H]muscimol binding to GABA sites as studied by ligand autoradiography was reduced in various brain regions of delta(-/-) animals. [(3)H]Ro 15-4513 binding to benzodiazepine sites was increased in delta(-/-) animals, partly due to an increment of diazepam-insensitive receptors, indicating an augmented forebrain assembly of gamma 2 subunits with alpha 4 subunits. In the western blots of forebrain membranes of delta(-/-) animals, the level of gamma 2 subunit was increased and that of alpha …
Beta‐blockers withdrawal in patients with heart failure with preserved ejection fraction and chronotropic incompetence: Effect on functional capacity…
2020
Abstract Background The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has emerged as a crucial pathophysiological mechanism. Beta‐blockers, drugs with negative chronotropic effects, are commonly used in HFpEF, although current evidence does not support its routine use in these patients. Hypothesis We postulate beta‐blockers may have deleterious effects in HFpEF and ChI. This work aims to evaluate the short‐term effect of beta‐blockers withdrawal on functional capacity assessed by the maximal oxygen uptake (peakVO2) in patients with HFpEF and ChI. Methods This is a prospective, crossover, randomized (1…
Behavioral analysis indicates benzodiazepine-tolerance mediated by the benzodiazepine binding-site at the GABA(A)-receptor.
2001
Abstract 1. GABA A -receptor induced changes in locomotion and anxiety-like behaviors were studied in rats using an open-field and an elevated plus-maze. Acute and chronic doses of the benzodiazepine diazepam without and in combination with the GABA uptake inhibitor SKF-89976A were investigated. 2. Fifty-six male rats of the strain PVG/OlaHsd (PVG; 180–200g body wt) were used to assess the influence of the benzodiazepine binding-site to the development of tolerance. Rats were divided into six groups: The first receiving saline (0.9%), the second and third diazepam (10.0 mg/kg) daily for 23 days with or without an acute challenge of 2.0 mg/kg diazepam. The fourth group received diazepam (10.…
In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain
2012
The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA A receptor. To visualize BDZ site availability, [C-11]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [C-11]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduce…
Beta-carbolines as benzodiazepine receptor ligands II: Synthesis and benzodiazepine receptor affinity of beta-carboline-3-carboxylic acid amides.
1985
Numerous beta-carboline-3-carboxamides were synthesized by amidation of beta-carboline-3-carboxylic acid, with various amino acids and amino acid esters serving as amine components, and tested in respect to their affinity for the benzodiazepine receptor in mouse brain membranes. The title compounds have affinities in the low micromolar range. The results are discussed with respect to their relevance for a possible beta-carboline structure containing the endogenous ligand of the benzodiazepine receptor.