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Clinical and experimental use of ketamine in psychiatry
Rydzyková, Tereza ; Tylš, Filip (advisor) ; Melkes, Barbora (referee)
Ketamine (NMDA receptor antagonist) is used primarily as an anesthetic in medicine. This paper deals with the use of ketamine in psychiatric research. A brief section approaching pharmacology and neurobiological effects of this substance, is followed by the main essay dealing within the first part with the use of ketamine as a potential new antidepressant drug. Preclinical and clinical studies demonstrating the effectiveness of this substance are described. Than neurobiological mechanisms underlying antidepressant action of ketamine are discussed. The second part of this review focuses on the use of ketamine as a pharmacological model of psychosis. Also published animal studies and studies administering ketamine in healthy subjects and schizophrenic patients are outlined. Subsequently neurobiological mechanism by which ketamine induces a psychotic state is proposed. Key words: Ketamine, NMDA receptor, schizophrenia, treatment-resistant depression, model of psychosis, antidepressant drug
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Effects of Neurotransmission-Modulating Multipotent Compounds in Pharmacological Animal Models of Cognitive Deficit
Chvojková, Markéta ; Valeš, Karel (advisor) ; Kuchař, Martin (referee) ; Rudá, Jana (referee)
In preclinical research on Alzheimer's disease pharmacotherapy, attention is paid to multipotent compounds, enabling intensification of the effect by targeting multiple pathophysiological mechanisms. The aim of the thesis was to assess the effect of multipotent compounds and combination therapy in models of cognitive deficit in the rat. The mechanism of action of the tested compounds was modulation of neurotransmitter systems. The aim of the first part of the study was to compare the effect of experimental monotherapy and combination therapy with an N-methyl-D-aspartate (NMDA) receptor antagonist and a γ-aminobutyric acid type A (GABAA) receptor positive modulator in the trimethyltin-induced model. Superiority of the combination therapy was proven by histological analysis of hippocampal neurodegeneration; however, it did not reach statistical significance in the cognitive test. The other part of the thesis focused on multipotent tacrine derivatives. We demonstrated a positive effect of 6- chlorotacrine-6-nitrobenzothiazole hybrid, as well as 6-chlorotacrine-L-tryptophan hybrid, acting as acetylcholinesterase inhibitors, in the scopolamine-induced model of cognitive deficit. Besides, we demonstrated a low risk of serious side effects of other tacrine derivatives acting as NMDA receptor antagonists....
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Clinical and experimental use of ketamine in psychiatry
Rydzyková, Tereza ; Tylš, Filip (advisor) ; Melkes, Barbora (referee)
Ketamine (NMDA receptor antagonist) is used primarily as an anesthetic in medicine. This paper deals with the use of ketamine in psychiatric research. A brief section approaching pharmacology and neurobiological effects of this substance, is followed by the main essay dealing within the first part with the use of ketamine as a potential new antidepressant drug. Preclinical and clinical studies demonstrating the effectiveness of this substance are described. Than neurobiological mechanisms underlying antidepressant action of ketamine are discussed. The second part of this review focuses on the use of ketamine as a pharmacological model of psychosis. Also published animal studies and studies administering ketamine in healthy subjects and schizophrenic patients are outlined. Subsequently neurobiological mechanism by which ketamine induces a psychotic state is proposed. Key words: Ketamine, NMDA receptor, schizophrenia, treatment-resistant depression, model of psychosis, antidepressant drug
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