piperidines and tianeptine

In ex vivo experiments, tianeptine increased serotonin uptake in the hippocampus and the cortex acutely and after 72 hours following chronic administration for 15 days. This effect results from an increased maximal rate of uptake without changes in the number or affinity to binding sites for I'3H-imipramine or I'3H-paroxetin. In addition, tianeptine increased extracellular levels of 5-hydroxyindolacetic acid (5-HIAA) in hippocampus and hypothalamus measured with in vivo voltametry. It can thus be concluded that tianeptine also raises 5-hydrotryptamine (5HT) uptake in vivo. The effects of tianeptine on the serotoninergic system, especially the increase in serotonin uptake, are discussed in relation with its effects on behaviour and the dopaminergic and cholinergic systems.

Topics: Animals; Antidepressive Agents; Antidepressive Agents, Tricyclic; Cerebral Cortex; Cyclic AMP; Hippocampus; Hydroxyindoleacetic Acid; Hypothalamus; Injections, Intraperitoneal; Paroxetine; Piperidines; Rats; Serotonin; Thiazepines

Inappropriate verbal and physical sexual behaviour is not common among individuals with dementia, but when it does occur, it can have profound consequences. We report a case of 79-year-old woman with dementia of the Alzheimer's type who complained of increased libido after an increased dose of donepezil, which was being used along with tianeptine. Donepezil withdrawal led to the resolution of increased libido, but when it was reintroduced, increased libido reappeared once again (Naranjo score: 7). Increased libido was not reported by the patient during the 6-year follow-up period after donepezil withdrawal. A potential mechanism of acetylcholinesterase inhibitor-induced increased libido and the current literature on hypersexuality as a side-effect of donepezil treatment are discussed.

Topics: Alzheimer Disease; Antidepressive Agents, Tricyclic; Cholinesterase Inhibitors; Donepezil; Dose-Response Relationship, Drug; Female; Humans; Indans; Libido; Piperidines; Sleep Initiation and Maintenance Disorders; Thiazepines; Treatment Outcome

The main objective of our study was to evaluate the influence of traxoprodil on the activity of the atypical antidepressant drugs (agomelatine, mianserin, tianeptine).. The forced swim test (FST) in mice was used to determine the antidepressant-like activity of the tested agents. Drugs levels in brain tissue were assessed by a high performance liquid chromatography method.. Concurrent intraperitoneal administration of per se ineffective doses of traxoprodil (10mg/kg) and agomelatine (20mg/kg) shortened the immobility time of animals in the FST. The observed effect was associated with elevated brain levels of traxoprodil. Similar interaction was not detected for traxoprodil and mianserin (10mg/kg) or tianeptine (15mg/kg).. Traxoprodil-agomelatine interaction is pharmacokinetic in nature. A combination of these agents has a potential to become an interesting strategy in the treatment of depression.

Topics: Acetamides; Animals; Antidepressive Agents; Brain; Depression; Depressive Disorder; Drug Synergism; Male; Mianserin; Mice; Motor Activity; Piperidines; Swimming; Thiazepines

Respiratory depression remains an important clinical problem that limits the use of opiate analgesia. Activation of AMPA glutamate receptors has been shown to reverse fentanyl-induced respiratory changes. Here, we explored whether tianeptine, a drug known for its ability to phosphorylate AMPA receptors, can be used to prevent opiate-induced respiratory depression. A model of respiratory depression in conscious rats was produced by administration of morphine (10mg/kg, i.p.). Rats were pre-treated with test compounds or control solutions 5min prior to administration of morphine. Respiratory activity was measured using whole-body plethysmography. In conscious animals, tianeptine (2 and 10mg/kg, ip) and DP-201 (2-(4-((3-chloro-6-methyl-5,5-dioxido-6,11-dihydrodibenzo[c,f][1,2] thiazepin-11-yl)amino)butoxy)acetic acid; tianeptine analogue; 2mg/kg, ip) triggered significant (~30%) increases in baseline respiratory activity and prevented morphine-induced respiratory depression. These effects were similar to those produced by an ampakine CX-546 (15mg/kg, ip). The antinociceptive effect of morphine (hot plate test) was unaffected by tianeptine pre-treatment. In conclusion, the results of the experiments conducted in conscious rats demonstrate that systemic administration of tianeptine increases respiratory output and prevents morphine-induced respiratory depression without interfering with the antinociceptive effect of opiates.

Topics: Animals; Dioxanes; Dioxoles; Disease Models, Animal; Excitatory Amino Acid Agonists; Lung; Male; Morphine; Pain Threshold; Phosphorylation; Piperidines; Plethysmography, Whole Body; Rats, Sprague-Dawley; Receptors, AMPA; Respiration; Respiratory Insufficiency; Thiazepines; Time Factors

According to reports in the literature, more than 30% of depressive patients fail to achieve remission. Therapy with the conventional antidepressant drugs may induce the serious adverse reactions. Moreover, its benefits may be seen at least 2-4 weeks after the first dose. Therefore, the alternative strategies for prevention and treatment of depression are sought. The main aim of our study was to assess the effects of ifenprodil given at a non-active dose (10mg/kg) on the activity of antidepressant agents from diverse pharmacological groups.. The antidepressant-like effect was assessed by the forced swim test in mice.. Ifenprodil potentiated the antidepressant-like effect of imipramine (15mg/kg) and fluoxetine (5mg/kg) while did not reduce the immobility time of animals which simultaneously received reboxetine (2.5mg/kg) or tianeptine (15mg/kg).. The concomitant administration of certain commonly prescribed antidepressant drugs that affect the serotonergic neurotransmission (i.e., typical tricyclic antidepressants and selective serotonin reuptake inhibitors) with a negative modulator selectively binding to the GluN1/N2B subunits of the NMDA receptor complex (i.e., ifenprodil) may induce a more pronounced antidepressant-like effect than monotherapy. However, these findings still need to be confirmed in further experiments.

Topics: Animals; Antidepressive Agents; Depression; Disease Models, Animal; Drug Synergism; Fluoxetine; Imipramine; Mice; Morpholines; Piperidines; Reboxetine; Swimming; Thiazepines

Adult neurogenesis has been implicated in affective disorders and the action of antidepressants (ADs) although the functional significance of this association is still unclear. The use of animal models closely mimicking human comorbid affective and anxiety disorders seen in the majority of patients should provide relevant novel information. Here, we used a unique genetic mouse model displaying higher trait anxiety (HAB) and comorbid depression-like behavior. We demonstrate that HABs have a lower rate of hippocampal neurogenesis and impaired functional integration of newly born neurons as compared with their normal anxiety/depression-like behavior (NAB) controls. In HABs, chronic treatment with the AD fluoxetine alleviated their higher depression-like behavior and protected them from relapse for 3 but not 7 weeks after discontinuation of the treatment without affecting neurogenesis. Similar to what has been observed in depressed patients, fluoxetine treatment induced anxiogenic-like effects during the early treatment phase in NABs along with a reduction in neurogenesis. On the other hand, treatment with AD drugs with a particularly strong anxiolytic component, namely the neurokinin-1-receptor-antagonist L-822 429 or tianeptine, increased the reduced rate of neurogenesis in HABs up to NAB levels. In addition, challenge-induced hypoactivation of dentate gyrus (DG) neurons in HABs was normalized by all three drugs. Overall, these data suggest that AD-like effects in a psychopathological mouse model are commonly associated with modulation of DG hypoactivity but not neurogenesis, suggesting normalization of hippocampal hypoactivity as a neurobiological marker indicating successful remission. Finally, rather than to higher depression-related behavior, neurogenesis seems to be linked to pathological anxiety.

Topics: Analysis of Variance; Animals; Antidepressive Agents; Anxiety; Behavior, Animal; Biomarkers; Dentate Gyrus; Depression; Disease Models, Animal; Female; Fluoxetine; Mice; Neurogenesis; Piperidines; Recurrence; Remission Induction; Thiazepines