olanzapine and tianeptine

Chronic stress which can cause a variety of disorders and illness ranging from metabolic and cardiovascular to mental leads to alterations in content, structure and dynamics of biomolecules in brain. The determination of stress-induced changes along with the effects of antidepressant treatment on these parameters might bring about more effective therapeutic strategies. In the present study, we investigated unpredictable chronic mild stress (UCMS)-induced changes in biomolecules in mouse brain and the restoring effects of tianeptine (TIA), olanzapine (OLZ) and fluoxetine (FLX) on these variations, by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that chronic stress causes different membrane packing and an increase in lipid peroxidation, membrane fluidity. A significant increment for lipid/protein, C=O/lipid, CH3/lipid, CH2/lipid, PO(-)2/lipid, COO(-)/lipid and RNA/protein ratios but a significant decrease for lipid/protein ratios were also obtained. Additionally, altered protein secondary structure components were estimated, such as increment in random coils and beta structures. The administration of TIA, OLZ and FLX drugs restored these stress-induced variations except for alterations in protein structure and RNA/protein ratio. This may suggest that these drugs have similar restoring effects on the consequences of stress activity in brain, in spite of the differences in their action mechanisms. All findings might have importance in understanding molecular mechanisms underlying chronic stress and contribute to studies aimed for drug development.

Topics: Animals; Antidepressive Agents; Benzodiazepines; Brain; Brain Chemistry; Fluoxetine; Lipid Peroxidation; Male; Membrane Fluidity; Mice; Mice, Inbred BALB C; Olanzapine; Stress, Psychological; Thiazepines

Strong evidence indicates that impaired cognition is a core element of depression, and antidepressant treatment may ameliorate cognitive impairments experienced by depressive patients. Present study was performed to investigate effects of chronic tianeptine (5 mg/kg) or olanzapine (2.5 mg/kg) administration on cognitive behaviors of unpredictable chronic mild stress (UCMS)-exposed mice and to compare these effects to those induced by widely used SSRI antidepressant fluoxetine (15 mg/kg) in mice.. To investigate effects of these drugs, the Morris water maze test (MWM), elevated plus maze test (EPM) and radial arm maze test (RAM) were used. The effects of stress and drugs on gene expression in the hippocampus was determined by quantitative Real Time-PCR.. In MWM test, fluoxetine significantly increased escape latency of non-stressed mice in acquisition sessions and decreased time spent in escape platform quadrant in probe trial; tianeptine and olanzapine decreased enhancement in escape latency, and only olanzapine significantly enhanced attenuation in time spent in the escape platform quadrant in UCMS-exposed mice. In EPM test, all drugs significantly decreased enhancement in transfer latency in UCMS-exposed mice. In RAM test, fluoxetine significantly increased number of errors made by both non-stressed and UCMS-exposed mice.. Quantitative real-time PCR revealed that CREB and BDNF gene expression levels were significantly decreased in UCMS-exposed group, and this effect was significantly reversed by each of drugs tested. Our results seem to be test dependent and should be further investigated using different learning and memory tasks.

Topics: Animals; Benzodiazepines; Brain-Derived Neurotrophic Factor; Cognition; Cyclic AMP Response Element-Binding Protein; Fluoxetine; Male; Maze Learning; Memory; Mice; Mice, Inbred BALB C; Olanzapine; Selective Serotonin Reuptake Inhibitors; Stress, Psychological; Thiazepines

Tianeptine is an atypical antidepressant drug that has a different mechanism of action than other antidepressants. Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia. The present study was undertaken to investigate effects of chronic administration of tianeptine or olanzapine on unpredictable chronic mild stress (UCMS)-induced depression-like behavior in mice compared to a widely used SSRI antidepressant, fluoxetine.. Male inbred BALB/c mice were subjected to different kinds of stressors several times a day for 7weeks and were treated intraperitoneally with tianeptine (5mg/kg), olanzapine (2.5mg/kg), fluoxetine (15mg/kg) or vehicle for 5weeks (n=7-8 per group).. All the drugs tested prevented stress-induced deficit in coat state during UCMS procedure, in grooming behavior in the splash test, decreased the attack frequency in the resident intruder test and decreased the immobility time in the tail suspension test. In the open field test olanzapine had anxiolytic-like effects in both stressed and non-stressed mice. Tianeptine, olanzapine and fluoxetine decreased the enhanced levels of plasma ACTH and IL-6. Chronic treatment with tianeptine resulted in a significant increase in both total number and density of BrdU-labeled cells in stressed animals, while fluoxetine and olanzapine had a partial effect.. The results of this study support the hypothesis that tianeptine can be as effective as fluoxetine for the treatment of depression in spite of the differences in the mechanism of action of these drugs. Moreover, olanzapine could be used effectively in psychotic patients with depression.

Topics: Adrenocorticotropic Hormone; Animals; Antidepressive Agents; Behavior, Animal; Benzodiazepines; Depression; Disease Models, Animal; Fluoxetine; Injections, Intraperitoneal; Interleukin-6; Male; Mice; Mice, Inbred BALB C; Olanzapine; Stress, Psychological; Thiazepines

Monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters, has an important role in the brain development and function, and MAO inhibitors have a range of potential therapeutic uses. We investigated systematically in vitro effects of pharmacologically different antidepressants and mood stabilizers on MAO activity.. Effects of drugs on the activity of MAO were measured in crude mitochondrial fraction isolated from cortex of pig brain, when radiolabeled serotonin (for MAO-A) or phenylethylamine (for MAO-B) was used as substrate. The several antidepressants and mood stabilizers were compared with effects of well known MAO inhibitors such as moclobemide, iproniazid, pargyline, and clorgyline.. In general, the effect of tested drugs was found to be inhibitory. The half maximal inhibitory concentration, parameters of enzyme kinetic, and mechanism of inhibition were determined. MAO-A was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > desipramine > amitriptyline > imipramine > citalopram > venlafaxine > reboxetine > olanzapine > mirtazapine > tianeptine > moclobemide, cocaine >> lithium, valproate. MAO-B was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > venlafaxine > amitriptyline > olanzapine > citalopram > desipramine > reboxetine > imipramine > tianeptine > mirtazapine, cocaine >> moclobemide, lithium, valproate. The mechanism of inhibition of MAOs by several antidepressants was found various.. It was concluded that MAO activity is acutely affected by pharmacologically different antidepressants at relatively high drug concentrations; this effect is inhibitory. There are differences both in inhibitory potency and in mechanism of inhibition between both several drugs and the two MAO isoforms. While MAO inhibition is not primary biochemical effect related to their therapeutic action, it can be supposed that decrease of MAO activity may be concerned in some effects of these drugs on serotonergic, noradrenergic, and dopaminergic neurotransmission.

Topics: Affect; Amitriptyline; Animals; Antidepressive Agents; Antimanic Agents; Benzodiazepines; Cerebral Cortex; Citalopram; Clorgyline; Cocaine; Cyclohexanols; Desipramine; Fluoxetine; Imipramine; In Vitro Techniques; Iproniazid; Lithium; Mianserin; Mirtazapine; Mitochondria; Moclobemide; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Morpholines; Olanzapine; Pargyline; Reboxetine; Swine; Thiazepines; Valproic Acid; Venlafaxine Hydrochloride