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Effects of antidepressants and depressive disorders on mitochondrial functions
Hroudová, Jana ; Fišar, Zdeněk (advisor)
Mood disorders are serious diseases. Nevertheless, their pathophysiology is not sufficiently clarified. Biological markers that would facilitate the diagnosis or successful prediction of pharmacotherapy are still being sought. The aim of the study was to find out whether mitochondrial functions are affected by antidepressants, mood stabilizers and depression. Our research is based on recent hypotheses of mood disorders, the advanced monoamine hypothesis, the neurotrophic hypothesis, and the mitochondrial dysfunction hypothesis. We assume that impaired function of mitochondria leads to neuronal damage and can be related to the origin of mood disorders. Effects of antidepressants and mood stabilizers on mitochondrial functions can be related to their therapeutic or side effects. In vitro effects of pharmacologically different antidepressants and mood stabilizers on the activities of mitochondrial enzymes were measured in mitochondria isolated from pig brains (in vitro model). Activity of monoamine oxidase (MAO) isoforms was determined radiochemically, activities of other mitochondrial enzymes were measured spectrophotometrically. Overall activity of the system of oxidative phosphorylation was measured electrochemically using high- resolution respirometry. Methods were modified to measure the same...
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Effects of antidepressants and depressive disorders on mitochondrial functions
Hroudová, Jana ; Fišar, Zdeněk (advisor) ; Martásek, Pavel (referee) ; Kuča, Kamil (referee)
Mood disorders are serious diseases. Nevertheless, their pathophysiology is not sufficiently clarified. Biological markers that would facilitate the diagnosis or successful prediction of pharmacotherapy are still being sought. The aim of the study was to find out whether mitochondrial functions are affected by antidepressants, mood stabilizers and depression. Our research is based on recent hypotheses of mood disorders, the advanced monoamine hypothesis, the neurotrophic hypothesis, and the mitochondrial dysfunction hypothesis. We assume that impaired function of mitochondria leads to neuronal damage and can be related to the origin of mood disorders. Effects of antidepressants and mood stabilizers on mitochondrial functions can be related to their therapeutic or side effects. In vitro effects of pharmacologically different antidepressants and mood stabilizers on the activities of mitochondrial enzymes were measured in mitochondria isolated from pig brains (in vitro model). Activity of monoamine oxidase (MAO) isoforms was determined radiochemically, activities of other mitochondrial enzymes were measured spectrophotometrically. Overall activity of the system of oxidative phosphorylation was measured electrochemically using high- resolution respirometry. Methods were modified to measure the same...
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The effect of psychotropic drugs on the mitochondrial functions.
Cikánková, Tereza ; Rečková Hroudová, Jana (advisor) ; Herink, Josef (referee) ; Vaňhara, Petr (referee)
Psychopharmaca are a large group of drugs widely used not only in psychiatry. Their systemic administration affects both the main diagnosis and the organism as a whole. The subject of our experiments is the effect of psychopharmaca on the changes in mitochondrial functions, which is beneficial for understanding of molecular mechanisms of therapeutic and adverse effects of drugs. The aim of this thesis was to study the in vitro effects of selected drugs on the cell energy metabolism. Selected antipsychotics (chlorpromazine, levomepromazine, haloperidol, risperidone, ziprasidone, zotepine, aripiprazole, clozapine, olanzapine, and quetiapine), antidepressants (bupropion, fluoxetine, amitriptyline, imipramine) and mood stabilizers (lithium, valproate, valpromide, lamotrigine, carbamazepine) were tested. In vitro effects of selected psychopharmaca were measured on isolated pig brain mitochondria. The activities of citrate synthase (CS) and electron transport chain (ETC) complexes (I, II+III, IV) were measured spectrophotometrically. Drug-induced changes of mitochondrial respiration rates linked to complex I (supported by malate and pyruvate) and complex II (supported by succinate) were evaluated by high resolution respirometry. Complex I was significantly inhibited by lithium, carbamazepine, fluoxetine,...
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SSRI Antidepressant Consumption in Czech Republic
Behrová, Júlia ; Horký, Pavel (advisor) ; Rejmanová, Anna (referee)
SSRI antidepressant consumption in Czech republic Author: Júlia Behrová Supervisor: PharmDr. Pavel Horký, PhD. Consultant: PharmDr. Eva Zimčíková, Ph.D Introduction: Selective serotonin reuptake inhibitors increase the available amount of neurotransmitter serotonin in synapses, resulting in their antidepressant and anxiolytic effect. Objective: The objective of this diploma thesis was to evaluate the consumption of SSRI antidepressants in the Czech Republic in the period from 01. 01. 2008 - 31. 12. 2018, based on the data on consumption from the State Institute of Drug Control (SIDC). Methods: The research consisted of a retrospective analysis of the SIDC database. The study included all approved SSRI in the Czech Republic. Drug Utilization Review was used in the thesis as a methodology. Drug consumption is calculated as the number of defined daily doses per thousand inhabitants per day (DID). The data on the number of residents was acquired from the Czech Statistical Office. Descriptive statistics and ATC/DDD methodology were applied. Results: The consumption of sertraline and escitalopram increased significantly during the period under review. For sertraline, the DID increased from an initial 8.623 to 15.513, increasing consumption by 1.8 fold. The greatest increase in consumption was observed...
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Dual Antidepressant Consumption in Czech Republic
Čiháková, Kristýna ; Horký, Pavel (advisor) ; Malý, Josef (referee)
Dual Antidepressant Consumption in the Czech Republic Author: Kristýna Čiháková Supervisor: PharmDr. Pavel Horký, Ph.D. Consultant: PharmDr. Kateřina Malá, Ph.D. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Introduction: Antidepressants are widely used in many indications. Dual antidepressants are prescribed in treatment of depressive disorder, anxiety disorder, in pain therapy and insomnia. Besides that, there are trials to prove the efficacy of dual antidepressants in different indications. Generally, antidepressant consumption in the Czech Republic is increasing. The question is, what the real proportion of dual antidepressant consumption is. Objective: As the objective, dual antidepressant consumption was analysed. Methods: The consumption of antidepressants venlafaxine, duloxetine, mirtazapine and mianserin was performed in the period from 1 January 2008 to 31 December 2018. The State Institute for Drug Control (SÚKL) database was used. The data were described by descriptive statistics. The drug consumption in Defined Daily Doses (DDD) was converted into Defined Daily Dose/1,000 inhabitants/day (DID). In addition, comparison of use of particular dual antidepressant doses was made. Results: Overall, the relative consumption of dual...
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The influence of antidepressants on serotonin homeostasis in placenta
Váchalová, Veronika ; Štaud, František (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Veronika Váchalová Supervisor: Prof. PharmDr. František Štaud, Ph.D. Consultant: Mgr. Rona Karahoda Title of diploma thesis: The influence of antidepressants on serotonin homeostasis in placenta Depression is a serious mental disorder affecting 10-20% of women during pregnancy. Up to 10% of these pregnant women are prescribed antidepressants (ADs), most frequently from the class of selective serotonin (5-HT) reuptake inhibitors (SSRIs). While the safety of this treatment is questionable due to reported impaired pregnancy/fetal outcomes, understanding of potential mechanistic causes is still lacking. During pregnancy, 5-HT is important for normal placental function and proper fetal development and programming. 5-HT homeostasis in the placenta is maintained via the 5-HT transporter (SERT/SLC6A4) on the apical side and the recently characterized organic cation transporter 3 (OCT3/SLC22A3) on the basal side of trophoblast. These transporters take up 5-HT from the maternal and fetal circulations, respectively into the syncytiotrophoblast (STB) where it is degraded by monoamine oxidase-A (MAO-A). As all ADs interfere with the 5-HT system it is important to study their potential interactions in the...
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Molecular mechanisms of action of antidepressants.
Brenišin, Martin ; Hejnová, Lucie (advisor) ; Valeš, Karel (referee)
Depression is a widely spread medical illness which affects people's thoughts, moods, physical health and general quality of their lives. Typical symptoms of this disorder are bad mood, lack of energy, sadness, insomnia or disability to feel happiness and enjoy life. Most people have encountered depression either directly or indirectly, through their family members or close friends. Number of patients with major depressive disorder grows globally every year. As much as half of the patients have got suicidal thoughts during their depressive episode while a quarter of them have tried to commit suicide. Therefore, the treatment of depression is very important. Antidepressants represent a large group of drugs focused on that treatment. Nowadays, there is a lot of antidepressants with different mechanism of action, their main effect being the increase in levels of monoamine neurotransmitters in brain. Selective reuptake inhibitors achieve this by blocking transporters of said neurotransmitters. Another type of antidepressants inhibits the activity of monoamine oxidase, which degrades serotonin, noradrenaline and dopamine. This paper reviews basic knowledge about main types of antidepressants and their mechanism of action. Key words: antidepressants, serotonin, depression, noradrenaline, monoamine...
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Antidepresiva - výskyt v přírodních vodách, účinky na organismy, možnosti jejich fototransformace v přírodním prostředí
ČERNÁ, Pavlína
The thesis is focused on one group of organic xenobiotic compounds, antidepressants, their presence in natural waters and their effects on aquatic organisms. A survey of increasing consumption of antidepressants in developed countries is presented together with numerous studies proving rising concentrations of these compounds in natural sufrace waters. Several studies dealing with influence of antidepressants on selected aquatic organisms of different trophic levels are demonstrated. Modern techniques, including AOPs (advanced oxidation processes), used for possible better waste waters treatment are discussed.
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Embryotoxicity testing of psychopharmacs using the CHEST method
Pavlovič, Ondřej ; Peterka, Miroslav (advisor) ; Maňáková, Eva (referee)
Psychotropic drugs are commonly used group of pharmaceuticals, their main effect is to alter psychic condition, including mental diseases treatment. Symptoms of mental illnesses are more and more common, theref orenumber of patients diagnosed with mental illnes, and thus using psychotropics, is growing stronger. But using psychotropics during gestation is not without risks for mother and embryo itself. However, thanks to the absence of controlled human studies, the knowledge of emrbyotoxic effects of pschotropics is limited to casuistics, reported side effects and animal experimental studies. Many of those studies suggests emrbyotoxic potential of psychotropic drugs, on the other hand, others claim their safety. The goal of this thesis is to test at least some of them, using CHEST method, that allows us to observe direct effect of unmetabolized substance on chick embryo. In this thesis we tested selected psychotropics, very common antidepressant fluoxetine (prozac) and antipsychotic drug olanzapine, for embryotoxicity, using in ovo method CHEST with chick embryos as model organism. By bypassing the maternal organism and his metabolism, this method allows to observe direct effect of unmetabolized substance on chick embryo. Results revealed embryotoxic effect of fluoxetin in dosage 10-2 and 10-3 on 3rd and...
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Effects of antidepressants and depressive disorders on mitochondrial functions
Hroudová, Jana ; Fišar, Zdeněk (advisor)
Mood disorders are serious diseases. Nevertheless, their pathophysiology is not sufficiently clarified. Biological markers that would facilitate the diagnosis or successful prediction of pharmacotherapy are still being sought. The aim of the study was to find out whether mitochondrial functions are affected by antidepressants, mood stabilizers and depression. Our research is based on recent hypotheses of mood disorders, the advanced monoamine hypothesis, the neurotrophic hypothesis, and the mitochondrial dysfunction hypothesis. We assume that impaired function of mitochondria leads to neuronal damage and can be related to the origin of mood disorders. Effects of antidepressants and mood stabilizers on mitochondrial functions can be related to their therapeutic or side effects. In vitro effects of pharmacologically different antidepressants and mood stabilizers on the activities of mitochondrial enzymes were measured in mitochondria isolated from pig brains (in vitro model). Activity of monoamine oxidase (MAO) isoforms was determined radiochemically, activities of other mitochondrial enzymes were measured spectrophotometrically. Overall activity of the system of oxidative phosphorylation was measured electrochemically using high- resolution respirometry. Methods were modified to measure the same...
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