Search results for "Muscarinic Antagonist"
showing 10 items of 90 documents
Stimulatory and inhibitory effects of ethanol on hippocampal acetylcholine release
1998
Using the microdialysis technique and sensitive HPLC procedures for the determination of acetylcholine (ACh) and ethanol, we investigated the release of ACh in rat hippocampus after acute ethanol administration. Systemic administration of ethanol (0.8 and 2.4 g/kg i.p.) led to peak ethanol concentrations of 21 and 42 mM in the hippocampus, respectively. The high dose caused a long-lasting inhibition of basal ACh release by up to 33%. Local infusion of scopolamine (1 microM) enhanced hippocampal ACh release up to eightfold in the presence of neostigmine (10 microM), and this stimulated release was also inhibited after systemic ethanol administration (by up to 45%). The low dose of ethanol (0…
Inhibitory and excitatory muscarinic receptors modulating the release of acetylcholine from the postganglionic parasympathetic neuron of the chicken …
1992
The effects of muscarinic receptor antagonists on ACh release were studied in the absence or presence of cholinesterase (ChE) inhibition using the isolated perfused chicken heart. Presynaptic inhibitory muscarinic autoreceptor were characterized by determining the potency of various antagonists to enhance [3H]-ACh release evoked by field stimulation (3 Hz, 1 min). The order of potencies was: (±)-telenzepine > atropine > 4-DAMP > silahexocyclium > pirenzepine > hexahydro-siladifenidol > AF-DX 116. The comparison with known pA2 values for M1-, M2- and M3-receptors revealed that the presynaptic autoreceptor meets the criteria of an M1-receptor. Basal, not electrically evoked overflow of unlabe…
Aclidinium inhibits human lung fibroblast to myofibroblast transition
2011
Background Fibroblast to myofibroblast transition is believed to contribute to airway remodelling in lung diseases such as asthma and chronic obstructive pulmonary disease. This study examines the role of aclidinium, a new long-acting muscarinic antagonist, on human fibroblast to myofibroblast transition. Methods Human bronchial fibroblasts were stimulated with carbachol (10 −8 to 10 −5 M) or transforming growth factor-β1 (TGF-β1; 2 ng/ml) in the presence or absence of aclidinium (10 −9 to 10 −7 M) or different drug modulators for 48 h. Characterisation of myofibroblasts was performed by analysis of collagen type I and α-smooth muscle actin (α-SMA) mRNA and protein expression as well as α…
GOLD 2017 treatment pathways in ‘real life’: An analysis of the DACCORD observational study
2017
Abstract Introduction The 2017 update to the Global Initiative for Obstructive Lung Disease (GOLD) strategy document includes recommendations for treatment intensification or step-down in chronic obstructive pulmonary disease (COPD), although recognises that limited supporting information is available. DACCORD is an ongoing observational, non-interventional study, recruiting patients following COPD maintenance treatment change or initiation, a subset of whom were receiving a long-acting β2-agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) on entry. Since there were no requirements in terms of prior medication (and no washout before commencing LABA/L…
Endothelial and neural factors functionally involved in the modulation of noradrenergic vasoconstriction in healthy pig internal mammary artery
2011
The role of endothelial and neural factors as modulators of neurogenic- and noradrenaline-induced vasoconstriction was examined in healthy pig internal mammary artery (IMA). Tetrodotoxin-, guanethidine-sensitive electrical field stimulation (EFS)-, and noradrenaline-elicited contractions were significantly diminished by prazosin (n=8, P0.001) and less so by rauwolscine, indicating functional α₁- and α₂-adrenoceptor-mediated noradrenergic innervation of the IMA. Endothelium removal reduced neurogenic (n=8, P0.01) but augmented noradrenaline responses (n=8, P0.01), suggesting the release of two endothelium-dependent factors with opposite effects. In the presence of endothelium, neurogenic and…
Why small particle fixed dose triple therapy? An excursus from COPD pathology to pharmacological treatment evolution
2022
Although bronchodilators are the cornerstone in chronic obstructive pulmonary disease (COPD) therapy, the treatment with a single-agent bronchodilator may not provide adequate symptoms control in COPD. The combination of drugs with different mechanisms of action may be more effective in inducing bronchodilation and preventing exacerbations, with a lower risk of side-effects in comparison with the increase of the dose of a single molecule. Several studies comparing the triple therapy with the association of long-acting ß2 agonist (LABA)/inhaled corticosteroid (ICS) or long-acting muscarinic antagonist (LAMA)/LABA reported improvement of lung function and quality of life. A significant reduc…
Pre- and Postsynaptic Effects of Muscarinic Antagonists in the Isolated Guinea Pig Ileum
1986
Several compounds have been claimed to differentiate between subtypes of muscarinic receptors (2). In the experiments described in this chapter we have studied in the guinea-pig ileum whether the presynaptic muscarinic receptors of the cholinergic nerves differ from the postsynaptic muscarinic receptors of the longitudinal muscle in their affinities for several muscarinic antagonists (methylatropine; trihexyphenidyl; clozapine; DAMP). Inhibition by oxotremorine of the evoked release of acetylcholine (ACh) was used as a parameter of presynaptic activity, and the increase by oxotremorine of smooth muscle tension as a postsynaptic parameter. The affinity constants (pA2 values) of the antagonis…
Cognitive and mood side effects of lower urinary tract medication
2019
Introduction: Muscarinic receptor antagonists, 5α-reductase inhibitors and α1-adrenoceptor antagonists are frequently used drug classes for the treatment of lower urinary tract symptoms including those of overactive bladder syndrome and benign prostatic enlargement/benign prostatic obstruction. Areas covered: The authors review the evidence for adverse effects of these drug classes on cognitive function, mood and other functions of the central nervous system and discuss such effects against the evidence for mechanistic plausibility. Expert opinion: Muscarinic antagonists carry a risk for impaired cognition and other brain functions that differs quantitatively between compounds, being highes…
Use of atropine-treated Daphnia magna survival for detection of environmental contamination by acetylcholinesterase inhibitors.
2003
The toxicity of cholinesterase-inhibiting compounds (e.g., carbamates and organophosphates) is due to a decrease in acetylcholine metabolism, which results in a continuous stimulation of cholinergic receptors (muscarinic and nicotinic) that can be fatal. The goal of this study was to evaluate the protective effect of atropine (muscarinic receptor antagonist) against paraoxon-induced toxicity to Daphnia magna using its survival rate for the detection of environmental contamination by cholinesterase-inhibiting compounds. As expected, paraoxon was lethal to D. magna in a concentration-dependent manner. Noteworthy, the pretreatment of these organisms with atropine dramatically increased their s…
Muscarinic inhibition of endogenous noradrenaline release from rabbit isolated trachea: receptor subtype and receptor reserve.
1994
The aim of the present study was to characterize putative muscarine receptors on sympathetic nerve terminals in the rabbit trachea. Release of endogenous noradrenaline from in vitro incubated rabbit trachea was evoked by electrical field stimulation (3 Hz, 540 pulses) and quantified by high performance liquid chromatography with electrochemical detection. The muscarine receptor agonist oxotremorine inhibited the evoked release of noradrenaline completely at 1 mumol/l (EC50: 64 nmol/l). The concentration response curve was very steep (Hill coefficient of 2.3). Scopolamine shifted the concentration response curve of oxotremorine to the right (-log KB 8.48) demonstrating specific, inhibitory m…