Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tianeptine, an atypical antidepressant that exhibits clinical efficacy in measures of depression and anxiety, has been reported to enhance learning and memory in rats under certain conditions, an effect not observed with other tricyclic antidepressants. The present study explores further the possibility that tianeptine or its enantiomers (S 16190 and S 16191) can enhance either learning or retention in animals in which the hippocampus has been made partially dysfunctional. The effects of tianeptine and its enantiomers were tested using an open field watermaze test, in rats with partial lesions of the medial septum/diagonal band of Broca (MSDB). When given to normal rats, tianeptine (10 mg/kg, i.p.) did not significantly affect learning as compared to animals injected with saline. We therefore created, in other animals, partial ibotenic acid lesions of MSDB and showed histochemically that these lesions reduced but did not abolish the density of acetylcholinesterase staining in the hippocampus. They impaired both the acquisition of place-navigation and the long-term retention of spatial information over 7 days. Against the baseline of impaired performance in animals with these lesions, neither tianeptine (10 mg/kg) nor its enantiomers (5 mg/kg) affected the rate of acquisition of place navigation. However, tianeptine did enhance the retention of spatial memory over 7 days. These results are discussed in relation to different effects that tianeptine may have on learning including its ability to block stress-induced dendritic re-modelling of the hippocampus.
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PMID:Tianeptine and its enantiomers: effects on spatial memory in rats with medial septum lesions. 1148 64

Tianeptine (37.5 mg/day) and paroxetine (20 mg/day) were compared in a population of depressive patients without past or current history of co-morbid anxiety and/or important anxiolytic treatment. In a 6-week, double blind trial, the special focus was on anxious symptoms.Both drugs showed good efficacy on depressive symptomatology, assessed with MADRS and HDRS, but no difference was detected between tianeptine and paroxetine, for any assessment criterion. Despite the choice of selected depressive patients, without any co-morbid anxious disorder, anxiety scale scores at inclusion (HAMA and BAS) were appreciable but correlated poorly with depressive scores. Both tianeptine and paroxetine improved the apparent anxious component in depression. Tolerability of both drugs was good, although significantly better with tianeptine.Thus tianeptine and paroxetine are effective and safe treatments for major depression and may also act directly on the anxious component of the psychopathology. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:Tianeptine and paroxetine in major depressive disorder, with a special focus on the anxious component in depression: an international, 6-week double-blind study dagger. 1240 74

Tianeptine was given to 30 patients aged 39-54 years with essential hypertension and masked, preclinical (n=29) or clinically evident (n=1) depression. This was associated with improvement of clinical psychiatric parameters and data of standardized questionnaire in 29 patients, and with decrease in frequency of hypertensive crises.
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PMID:[Therapy of affective disorders with tianeptine in patients with essential hypertension]. 1289 Dec 55

One hundred and forty two patients with ICD-10 diagnosis of depression from 7 research scientific were treated with tianeptine (coaxil); 124 have completed the treatment course. Moderate depression was diagnosed in 111 patients (89.5%) and severe depression--in 13 (10.5%). A duration of the last episode before treatment was 7.1 +/- 1.7 months. The mean score by Hamilton depression scale was 24.4 +/- 4.0. The patients received tianeptine as a monotherapy in dosage 12.5 mg, 3 times daily during 6 weeks (65-year olds and older were given 25 mg daily). Tianeptine proved to be an antidepressant with balanced action, i.e., exerted thymoanaleptic, anxiolytic and activating effects. The treatment was beneficial for 70.4% of the patients; remission was revealed in 58%. The medication was well tolerated with rare and weakly pronounced side effects.
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PMID:[Clinical efficacy and tolerability of tianeptine in treatment of depression (Russian open multicenter trial)]. 1456 74

The adult brain has more plasticity than previously believed. Neurogenesis, growth and branching of dendrites, and remodeling of synaptic contacts in different regions of the brain occur continuously. Numerous studies have reported a decrease in neuroplasticity in depressed patients and/or in animals subjected to stress and to different models of depression. This has led to the proposal of a new approach to the pathophysiology of depression: depression could be the result of the decrease in neuroplasticity in brain structures involved in the control of mood. This new approach to the pathophysiology of depression can lead to better understanding of, or the proposal of more solid hypotheses about, some issues such as the impact of genetics and environmental factors on the occurrence of depressive episodes, the increased risk of depression in patients with somatic diseases in which there are alterations of neuroplasticity, or the increased risk of depressive relapse in depressed patients in partial remission in whom we suspect that neuroplasticity is only partially restored. These observations have also led to the proposal of new hypotheses concerning the mode of action of antidepressant drugs. In this regard, tianeptine is of particular interest. Tianeptine's pharmacological and clinical properties have been extensively studied. Tianeptine has specific neurotrophic properties, and its antidepressant properties have been well demonstrated. Tianeptine provides early relief of anxious symptoms without sedation in depressed patients. The acceptability and safety profiles of tianeptine are appreciated by both physicians and patients; for instance, tianeptine does not induce sexual dysfunction, nausea, or weight gain. It is of interest to focus on what we already know about tianeptine's pharmacological and clinical properties, and to create mechanistic hypotheses about the similarities and differences observed in clinical practice between tianeptine and other antidepressants.
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PMID:From restoration of neuroplasticity to the treatment of depression: clinical experience. 1555 Mar 50

Neuronal plasticity is now known to be very important in the adult, both in the formation of new synaptic connections and of new neurones (neurogenesis) and of glial cells. However, old age and stress can inhibit this plasticity and lead to cerebral atrophy. The time course of changes in neuronal plasticity involves, in the first milliseconds to seconds, changes in synaptic strength (long term potentialisation, LTP, or long term depression, LTD), then, over minutes to hours, changes in the number of synaptic connections (linked to changes in neurotrophic factors), and over weeks to months, to changes in neuronal reconfiguration. These changes in brain systems are particularly targeted in psychiatric disorders to the areas which are sensitive to stress and play roles in memory and emotion (hippocampus, amygdala and prefrontal cortex). The discovery and development of drugs modifying neuronal plasticity and neurotrophins production has been a priority for Servier research for the last ten years; Servier has a clinically effective antidepressant, tianeptine (Stablon), with a favourable side effect profile, but which does not inhibit the uptake of serotonin, or other monoamines. However, this drug can reverse the deleterious effects of stress on neuronal plasticity, thereby acting on the causes of psychiatric disorders. Furthermore, a new research area is being investigated - facilitation of AMPA receptors, favouring the production of neurotrophic factors.
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PMID:[Synaptic plasticity and neuropathology: new approaches in drug discovery]. 1563 31

Depression is a common psychiatric problem in epileptic patients. Thus, it is important that an antidepressant agent has anticonvulsant activity. This study was organized to investigate the effects of tianeptine, an atypical antidepressant, on pentylenetetrazole (PTZ)-induced seizure in mice. A possible contribution of adenosine receptors was also evaluated. Adult male Swiss-Webster mice (25-35 g) were subjects. PTZ (80 mg/kg, i.p.) was injected to mice 30 min after tianeptine (2.5-80 mg/kg, i.p.) or saline administration. The onset times of 'first myoclonic jerk' (FMJ) and 'generalized clonic seizures' (GCS) were recorded. Duration of 600 s was taken as a cutoff time in calculation of the onset time of the seizures. To evaluate the contribution of adenosine receptors in the effect of tianeptine, a nonspecific adenosine receptor antagonist caffeine, a specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A2A receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) or their vehicles were administered to the mice 15 min before tianeptine (80 mg/kg) or saline treatments. Tianeptine (40 and 80 mg/kg) pretreatment significantly delayed the onset time of FMJ and GCS. Caffeine (10-60 mg/kg, i.p.) dose-dependently blocked the retarding effect of tianeptine (80 mg/kg) on the onset times of FMJ and GCS. DPCPX (20 mg/kg) but not CSC (1-8 mg/kg) blocked the effect of tianeptine (80 mg/kg) on FMJ. Our results suggest that tianeptine delayed the onset time of PTZ-induced seizures via adenosine A1 receptors in mice. Thus, this drug may be a useful choice for epileptic patients with depression.
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PMID:Effects of tianeptine on onset time of pentylenetetrazole-induced seizures in mice: possible role of adenosine A1 receptors. 1682 86

Tianeptine is an atypical antidepressant drug. In contrast to tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), it has been suggested that tianeptine decreases serotonin's activity and amount in serotonergic synapses of the central nervous system by increasing serotonin reuptake. Tianeptine, which has a mechanism of action opposite to that of SSRIs, necessitated a re-evaluation of the biochemical basis of depression and revealed that it cannot be explained by the monoamine hypothesis only. Recent studies by tianeptine have been focused on neuroplasticity. Neuroplasticity hypothesis of depression has the potential to make important contributions to the diagnosis, as well as it may be helpful in the explanation of the drug effects, which cannot be explained by neurochemical mechanisms. In addition, recent interesting results indicating anticonvulsant and analgesic activity of tianeptine and its possible interaction with adenosine A(1) receptors were obtained. In this review, novel central actions of tianeptine and the relationship between stress, neuroplasticity and drug effects were evaluated in the light of the current literature.
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PMID:Tianeptine: potential influences on neuroplasticity and novel pharmacological effects. 1782 81

The precise neurobiological processes involved in depression are not clear, but it is recognized that numerous factors are involved, including changes in neurotransmitter systems and brain plasticity. Neuroplasticity refers to the ability of the brain to adapt functionally and structurally to stimuli. Impairment of neuroplasticity in the hippocampus, amygdala and cortex is hypothesized to be the mechanism by which cognitive function, learning, memory and emotions are altered in depression. The mechanisms underlying alterations in neuroplasticity are believed to relate to changes in neurotransmitters, hormones and growth factors. Structural changes in the hippocampus that have been proposed to be associated with depression include dendritic atrophy, reduced levels of cerebral metabolites, decreased adult neurogenesis (generation of new nerve cells) and reduced volume. Increased dendritic branching occurs in the basolateral nucleus of the amygdala. Reduced neuronal size and glial cell density occur in the prefrontal cortex. Clinically, tianeptine is an antidepressant effective in reducing symptoms of depression in mild to moderate-to-severe major depression, including over the long term. Tianeptine is also effective in alleviating the symptoms of depression-associated anxiety. It is generally well tolerated, with little sedation or cognitive impairment. The efficacy profile of tianeptine could be explained by its neurobiological properties observed in animal models. Tianeptine prevents or reverses stress-associated structural and cellular changes in the brain and normalizes disrupted glutamatergic neurotransmission. In particular, in the hippocampus, it prevents stress-induced dendritic atrophy, improves neurogenesis, reduces apoptosis and normalizes metabolite levels and hippocampal volume. Tianeptine also has beneficial effects in the amygdala and cortex and can reverse the effects of stress on neuronal and synaptic functioning. The neurobiological properties of tianeptine may provide an explanation not only for its antidepressant activity, but also for its anxiolytic effects in depressed patients and its lack of adverse effects on cognitive function and memory.
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PMID:Neurobiological and clinical effects of the antidepressant tianeptine. 1807 12

Depression is associated with abnormal neuronal plasticity. AMPA receptors mediate transmission and plasticity at excitatory synapses in a manner which is positively regulated by phosphorylation at Ser831-GluR1, a CaMKII/PKC site, and Ser845-GluR1, a PKA site. Treatment with the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor fluoxetine increases P-Ser845-GluR1 but not P-Ser831-GluR1. Here, it was found that treatment with another antidepressant, tianeptine, increased P-Ser831-GluR1 in the frontal cortex and the CA3 region of hippocampus and P-Ser845-GluR1 in the CA3 region of hippocampus. A receptorome profile detected no affinity for tianeptine at any monaminergic receptors or transporters, confirming an atypical profile for this compound. Behavioural analyses showed that mice bearing point mutations at both Ser831- and Ser845-GluR1, treated with saline, exhibited increased latency to enter the centre of an open field and increased immobility in the tail-suspension test compared to their wild-type counterparts. Chronic tianeptine treatment increased open-field locomotion and reduced immobility in wild-type mice but not in phosphomutant GluR1 mice. P-Ser133-CREB was reduced in the CA3 region of hippocampus in phosphomutant mice, and tianeptine decreased P-Ser133-CREB in this region in wild-type, but not in phosphomutant, mice. Tianeptine increased P-Ser133-CREB in the CA1 region in wild-type mice but not in phosphomutant GluR1 mice. There were higher basal P-Ser133-CREB and c-fos levels in frontal and cingulate cortex in phosphomutant GluR1 mice; these changes in level were counteracted by tianeptine in a GluR1-independent manner. Using phosphorylation assays and phosphomutant GluR1 mice, this study provides evidence that AMPA receptor phosphorylation mediates certain explorative and antidepressant-like actions under basal conditions and following tianeptine treatment.
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PMID:Involvement of AMPA receptor phosphorylation in antidepressant actions with special reference to tianeptine. 1808 78


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