1st Faculty of Medicine Charles University 1st Faculty of Medicine Charles University Department of Psychiatry
msust 20.01.2011

Effect of pharmacologically selective antidepressants on synaptic signal transduction

Research Area:

  Addictions     Anxiety Disorders    Mood Disorders     Genomics   Psychopharmacology

  Eating Disorders    Psychophysiology    Neurodegenerative disorders                                    

 Cognitive Neuroscience    Schizophrenia    Traumatic stress   Social Psychiatry

Research project name:

Effect of pharmacologically selective antidepressants on synaptic signal transduction

(Joint project of Charles University in Prague and pharmaceutical company Zentiva a.s., Prague.)

Project Leader:

Raboch Jiří

People Involved:

Fišar Zdeněk, Hanuš Zdeněk, Kitzlerová Eva, Tvrzická Eva, Vecka Marek, Hansíková Hana, Amler Evžen, Ředinová Irena

Short project description:

Sensitivity of mitochondrial functions on in vitro administration of different antidepressants is measured in this project on model systems (synaptosomes or of peripheral blood components). We have got original results at study of effects of antidepressant on monoamine oxidase (MAO) activity, when we have observed inhibitory effects antidepressants belonging to the group of tricyclic antidepressant, selective serotonin or norepinephrine reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressant. These results support advanced monoamine theory of depression and imply, that both the kinetic of serotonin uptake, and MAO activity in blood platelets of depressive patient is possible to use as parameters suitable for characterization of subgroups of depressive disorder or for prediction of effects of treatment with antidepressants. Other results support bioenergetics model of affective disorders, which propose that mitochondrial functions could be common target of antidepressants with selective primary pharmacological effects.

Project goals:

The objective of the project is to discover, by means of study in vitro effects of different antidepressant, biological parameters suitable for next testing procedure as predictors of response on treatment with antidepressants or as biological markers of depressive disorder. We tested effects of antidepressants on series of actions connected with transmission of synaptic signal. We chose to be good for more detailed study the quantities influencing above all monoaminergic systems (transmembrane serotonin transport, monoamine oxidase activity, ATPase activity and next). We are studying action of antidepressants and mood stabilizers on mitochondrial functions (citric acid cycle, oxidative phosphorylation, etc.).

Project Milestones, Timing:

2005:  New methods were adopted which are necessary for project solution.

2006-2008:  Measurement followed of in vitro effects of different antidepressant and other psychotropics on selected biochemical and biophysical parameters in synaptosomes, mitochondria and blood cells (e.g. serotonin uptake, monoamine oxidase activity, ATPase activity, kinetics of oxygen consumption by mitochondria, membrane fluidity, membrane potential).

2008:  Experimental procedure will be designed, which will be applicable for study of individual differences in response to antidepressants at depressive patients.

2008-2010:  We will study in more detail the role of mitochondrial enzymes in mechanisms of action of psychotropic drugs (antidepressants, mood stabilizers, antipsychotics, drug abuse).

Possible Cooperation Mode:

 data gathering

 data analysis

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