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Evaluation of a novel series of [1,2,4] triazolo [4,3-a] quinoxalines and related compounds: highly potent adenosine receptor antagonists
Krpelíková, Irena ; Vopršalová, Marie (advisor) ; Macháček, Miloš (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology, Czech Republic Performed at: University of Bonn, Pharmaceutical Institute, Department of Pharmaceutical Chemistry, Germany Candidate: Irena Krpelíková Supervisors: Prof. Dr. Christa Elisabeth Müller PharmDr. Marie Vopršalová, CSc. Title of diploma thesis: Evaluation of a novel series of [1,2,4]triazolo[4,3- ɑ]quinoxalines and related compounds: highly potent adenosine receptor antagonists Adenosine, a local modulator, acts in many diverse biological processes. Its effects are mediated through adenosine receptors (ARs). Four types of ARs have been described, A1, A2A, A2B and A3, which belong to the superfamily of G protein-coupled receptors. AR ligands are being developed as new drugs. This thesis deals with the study of a novel series of [1,2,4]triazolo[4,3- a]quinoxalines and related compounds as potential adenosine receptor antagonists. The presented results were obtained using radioligand binding assays. Series of quinoxalinones and tetrazoloquinoxalines exhibit significant selectivity for human (h) A3 ARs but their affinity is relatively low for tetrazoloquinoxalines and moderate for quinoxalinones. Triazoloquinoxalines comprise the largest group of this series. Generally, the R1...
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The in vitro effects of selected isoflavonoids on isolated rat aorta
Novýsedláková, Alena ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Alena Novýsedláková Supervisor: PharmDr. Jana Pourová, PhD. Title of Thesis: In vitro effects od selected isoflavonoids on isolated rat aorta Abstract: The aim of this study was to determine whether the selected isoflavonoids are able to vasodilate aorta, what structural features might be responsible for a relaxing activity and estimate the mechanism of action. The experiment we carried out the classical in vitro method on the isolated rat aorta, and the results evaluated by the computer program GraphPad. Only glycitin did not show statistically significant relaxation of blood vessels, which can be attributed to ineffective glycosidic form. Other izoflavonoids- glycitein, daidzein and tectorigenin seem to be promising in terms of potential vasodilatation. Further studies would be needed to verify also the in vivo effects. Likely structural features include the hydroxy group at 7-position and a methoxy group at position 8 of the core od isoflavonoids. The mechanism of action is not yet known, but most likely appears endothelium-dependent mechanisms, alpha 1 receptor antagonism and agonism of muscarinic M3 receptor. It may be also involved in the effect of the antioxidant and...
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Elimination of alcohol in blood of patients treated with coumarin drugs
Kahounová, Jana ; Vopršalová, Marie (advisor) ; Trejtnar, František (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jana Kahounová Supervizor: Doc. PharmDr. Marie Vopršálová, Ph.D. Ing. Jaroslav Procházka Title of diploma thesis: ELIMINATION OF ALKOHOL IN BLOOD OF PATIENTS TREATED WITH COUMARIN DRUGS Coumarin preparations are the most commonly used oral anticoagulants. The main representative is Warfarin. The most important function of warfarin is to reduce the formation of K-dependent coagulation factors in the liver. Alcohol is the oldest and most widely used addictive substance. Alcohol is the oldest and most commonly used substance. Society is tolerated and regular use of small doses of alcohol is considered "beneficial to health". The aim of my thesis was to find out how the concomitant use of coumarin drugs and alcohol interacts. There were tested 62 people (33 men and 29 women), of whom 27 people (14 men and 13 women) were treated with coumarin drugs, 35 people (19 men and 16 women) formed the control group of individuals without treatment with coumarin drugs. All people were given a standard dose of alcohol. The blood alcohol level (COBAS INTEGRA 400 plus) and INR (SYSMEX CA 1500) were measured in the time-0 (before administration), 1½ and 3 hours (after administration). The data obtained was...
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The in vitro effects of selected isoflavonoids on isolated rat aorta
Novýsedláková, Alena ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Alena Novýsedláková Supervisor: PharmDr. Jana Pourová, PhD. Title of Thesis: In vitro effects od selected isoflavonoids on isolated rat aorta Abstract: The aim of this study was to determine whether the selected isoflavonoids are able to vasodilate aorta, what structural features might be responsible for a relaxing activity and estimate the mechanism of action. The experiment we carried out the classical in vitro method on the isolated rat aorta, and the results evaluated by the computer program GraphPad. Only glycitin did not show statistically significant relaxation of blood vessels, which can be attributed to ineffective glycosidic form. Other izoflavonoids- glycitein, daidzein and tectorigenin seem to be promising in terms of potential vasodilatation. Further studies would be needed to verify also the in vivo effects. Likely structural features include the hydroxy group at 7-position and a methoxy group at position 8 of the core od isoflavonoids. The mechanism of action is not yet known, but most likely appears endothelium-dependent mechanisms, alpha 1 receptor antagonism and agonism of muscarinic M3 receptor. It may be also involved in the effect of the antioxidant and...
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Effects of some flavonoids in isolated rat aortic rings
Pešková, Hana ; Vopršalová, Marie (advisor) ; Pourová, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Hana Pešková Supervisor: PharmDr. Marie Vopršalová, CSc. Title of diploma thesis: Effects of some flavonoids in isolated rat aortic rings Flavonoids with their wide range of effects are known for having positive influence on human health. It mainly concerns significant antioxidant and anti- inflammatory characteristics and cardiovascular diseases incidence reducing effects. The aim of this study was examination of vasorelaxant effects of selected flavonoids from isoflavonoid group: formononetin, isoformononetin, prunetin and ononin, occuring especially in Fabaceae family. The vasorelaxation potential of tested substances was examinated in in vitro conditions on isolated aortic rings of rat. The effect of increasing doses of individual flavonoids on preparation, with intact endothelium after previous precontraction with norepinefrine, was monitored (10-5 M). From measured values, there were DRC curves, EC50 values created and an evaluation was made. According to analysis of the results, the most significat activity has fromononetin (EC50 2,081 . 10-5 M) and isoformononetin (EC50 2,081, 10-5 M). Ononin showed almost no vasodilatory effect.
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The effect of quercetin and its selected metabolites on isolated aortal rings of rat
Šumpelová, Kateřina ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
v anglickém jazyce Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Mgr. Kateřina Šumpelová Supervisor: PharmDr. Marie Vopršalová, CSc. Title of rigorous thesis: The effect of quercetin and its selected metabolites on isolated aortal rings of rat Quercetin and it's metabolites are classified into the group of flavonoids. Flavonoid compounds are substances widely extended in nature. They below to the secondary metabolites of plants and have positive effect on live organism. Individual effects of flavonoids on the organism were described in this thesis, especially the effects on cardiovascular system. Flavonoids can have vasodilatory activity, antioxidant or anti-inflammatory effect. The experimental parts of the thesis dealing with the effect of quercetin and it's metabolites tamarixetin and isorhamnetin on isolated aortal rings of rat in vitro. Significant vasodilatory activity of these flavonoids was observed. The mechanism of the vasodilatory effect of qeurcetin was verified. Our experiments confirm the theory that the effect is independent on the function of endotel.
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Testing of transdermal permeation of selected xenobiotics
Stará, Veronika ; Herink, Josef (advisor) ; Vopršalová, Marie (referee)
This thesis first briefly mentions the characteristics of the skin and contains a review of current knowledge on the in vitro permeation testing of drugs through the skin. It describes the basic data about nerve agents and the possibilities of prophylaxis poisoning warfare agents focusing on preventive transdermal administration. The experimental work is focused on in vitro testing abilities oxime HI-6 and posibly other reactivators enzyme acetylcholinesterase penetrate through pig skin. Experiments were conducted in static diffusion cells Franz type. The amount of test substance leaked through the skin is determined in the sample of receptor fluid by HPLC. Keywords permeation in vitro; transdermal; pig skin; Franz cell; substance HI-6; antidota; nerve agents; acetylcholinesterase
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Comparison of efficacy of acetylcholinesterase inhibitors tacrine, rivastigmine and donepezil for the treatment of cognitive disorders induced by 3-quinuclidinyl benzylate in rat
Pavlíčková, Stela ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Mgr. Stela Pavlíčková Supervisor: PharmDr.Marie Vopršálová, CSc. Supervisor specialist: RNDr. Jan Misík, Ph.D. Title of rigorosa thesis: Comparison of efficacy of acetylcholinesterase inhibitors tacrine, rivastigmine and donepezil for the treatment of cognitive disorders induced by 3-quinuclidinyl benzylate in rat Alzheimer's disease is a severe neurodegenerative disorder connected with neuronal death, brain tissue loss and functional disruption of the cholinergic system. Pathophysiological changes are manifested especially as deterioration of memory and other cognitive functions. Current treatment consists mainly of pro-cognitive drugs - acetylcholinesterase inhibitors (previously - tacrine, today - donepezil, rivastigmine and galantamine) and NMDA (N-methyl-D- aspartate) antagonist memantine which can delay the disease progression. The aim of this study was to evaluate the therapeutic effect of three selected acetylcholinesterase inhibitors - tacrine, rivastigmine and donapezil on pharmacologically induced cognitive disorder in rats. As an amnesic drug, 3-quinuclidinyl benzilate was used and the effect of selected inhibitors was investigated using two different behavioral methods -...
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The effect of acetylcholinesterase reactivators on urinary bladder contraction
Rambousková, Lucia ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Candidate: Mgr. Lucia Rambousková Title of thesis: The effect of acetylcholinesterase reactivators on urinary bladder contraction Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Supervisor: PharmDr. Marie Vopršálová, CSc. Consultant specialist: PharmDr. Vendula Šepsová, Ph.D Acetylcholinesterase (AChE) reactivators major mechanism is attributed to their ability to reactivate phosporylated enzyme, AChE. It has been thought that oxime might have additional direct pharmacological effect, other than AChE reactivation. The oximes may exert effects by interaction with cholinergic receptors. The most of them have antiniconitic or antimuscarinic properties, thus they protect against higher concentration of acetylcholine. The aim of this study was to evaluate the effect of reactivators K 203 and K 027. A contraction study on the rat urinary bladder has been chosen to investigate effect on muscarinic and purinergic receptors. Isolated strips of urinary bladder in the organ bath were used. There were three types of stimulation - electric stimulation (EFS), muscarinic receptor agonist methacholine (MCh) and purinergic receptor agonist adenosine triphosphate (ATP). In conclusion oxime K 027 has tendency to reduce the contraction (during EFS and MCh...
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