FC13-09 - Antidepressant tianeptine (TIA) action is based on the acceleration of serotonin turnover in the synapse: a hypothesis

IntroductionNeurochemical mechanism of TIA action is not clear.AimTo develop possible mechanism of TIA action in patients with anxious depression (Uzbekov et al., 2006, 2009).ResultsIt was found twofold increase of platelet monoamine oxidase (MAO) activity in depressed patients and its significant decrease under TIA action.DiscussionSynapse is considered as a complex biological system (nerve ending + astrocytes). It is supposed that at normal conditions about 75% of serotonin released in synaptic cleft undergoes functional inactivation by its reuptake in presynaptic ending. The remaining serotonin is taken up by astroglia and is undergone its irreversible (chemical) inactivation under MAO action.According to our hypothesis TIA enhancing serotonin reuptake decreases serotonin level in synaptic cleft. Simultaneously in patients-responders we have established the decrease (inhibition) of MAO activity that promotes increase of serotonin concentration in synaptic cleft. It has been shown that TIA activates serotonin release from presynaptic ending (Labrid et al., 1992). Thus TIA enhances not only serotonin reuptake but simultaneously activates its surge from the ending into synaptic cleft. We conclude that under TIA action serotonin turnover rate in the synapse is increased that promotes increase in the unit of time serotonin concentration on postsynaptic receptors; this process is accompanied by decrease of MAO activity.ConclusionThe first time in the literature we propose the hypothesis about neurochemical mechanism of TIA action. Proposed mechanism mainly refers to the first acute phase of TIA action directed on the normalization of serotonergic neurotransmission.

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Alteration of Serotonin Release in the Guinea Pig Orbito-Frontal Cortex by Selective Serotonin Reuptake Inhibitors Relevance to Treatment of Obsessive-Compulsive Disorder

Neuropsychopharmacology ◽

10.1016/0893-133x(95)00045-f ◽

1995 ◽

Vol 13 (2) ◽

pp. 117-127 ◽

Cited By ~ 82

Author(s):

M El Mansari

Keyword(s):

Guinea Pig ◽

Frontal Cortex ◽

Obsessive Compulsive Disorder ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Serotonin Release ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

Obsessive Compulsive ◽

Compulsive Disorder

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An investigation into the effect of tryptophan on tail chewing behaviour of growing pigs

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200006906 ◽

2002 ◽

Vol 2002 ◽

pp. 34-34 ◽

Cited By ~ 7

Author(s):

J. McIntyre ◽

S.A. Edwards

Keyword(s):

Amino Acids ◽

Blood Brain Barrier ◽

Growing Pigs ◽

Serotonin Level ◽

Dietary Carbohydrate ◽

Serotonin Concentration ◽

Plasma Tryptophan ◽

And Control ◽

Chewing Behaviour ◽

Control Behaviour

Previous work (McIntyre and Edwards, 2001) revealed a significant correlation between plasma tryptophan (TRP) concentration and blood preference scores when pigs were fed a low CP diet. Increasing dietary TRP in rats causes increases in plasma and brain TRP, and brain serotonin concentration (Fernstrom and Wurtman, 1971), which appear to be highly localised to serotonin-containing neurones that may monitor the metabolic state and control behaviour. Uptake of TRP at the blood-brain barrier and serotonin level may also be increased by a higher TRP: LNAA (large neutral amino acids) ratio and level of dietary carbohydrate. This study aimed to determine if pigs fed diets differing in TRP and TRP: LNAA ratios differed in their behaviour or in their preference for blood during a model tail test.

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Acute selective serotonin reuptake inhibitors regulate the dorsal raphe nucleus causing amplification of terminal serotonin release

Journal of Neurochemistry ◽

10.1111/jnc.13528 ◽

2016 ◽

Vol 136 (6) ◽

pp. 1131-1141 ◽

Cited By ~ 12

Author(s):

Elyse C. Dankoski ◽

Susan Carroll ◽

Robert Mark Wightman

Keyword(s):

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Dorsal Raphe Nucleus ◽

Dorsal Raphe ◽

Serotonin Release ◽

Serotonin Reuptake Inhibitors ◽

Raphe Nucleus ◽

Selective Serotonin ◽

Dorsal Raphé

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Season as a Possible Confounding Factor in Reduced Brain Serotonin Turnover Following Selective Serotonin Reuptake Inhibitor Therapy

Archives of General Psychiatry ◽

10.1001/archpsyc.65.10.1224 ◽

2008 ◽

Vol 65 (10) ◽

pp. 1224

Author(s):

Fotios C. Papadopoulos

Keyword(s):

Selective Serotonin Reuptake Inhibitor ◽

Reuptake Inhibitor ◽

Serotonin Reuptake ◽

Confounding Factor ◽

Inhibitor Therapy ◽

Brain Serotonin ◽

Selective Serotonin ◽

Serotonin Reuptake Inhibitor ◽

Serotonin Turnover

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Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: Reduction by a selective serotonin reuptake inhibitor

Stress ◽

10.1080/10253890701300904 ◽

2007 ◽

Vol 10 (3) ◽

pp. 295-304 ◽

Cited By ~ 34

Author(s):

Murray Esler ◽

Elisabeth Lambert ◽

Marlies Alvarenga ◽

Florentia Socratous ◽

Jeff Richards ◽

...

Keyword(s):

Panic Disorder ◽

Selective Serotonin Reuptake Inhibitor ◽

Reuptake Inhibitor ◽

Serotonin Reuptake ◽

Panic Attack ◽

Brain Serotonin ◽

Selective Serotonin ◽

Serotonin Reuptake Inhibitor ◽

Serotonin Turnover

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The molecular and functional network in SSRI treatment

European Psychiatry ◽

10.1016/s0924-9338(11)73924-4 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 2222-2222

Author(s):

R. Lanzenberger

Keyword(s):

Extracellular Space ◽

Selective Serotonin Reuptake Inhibitors ◽

Therapeutic Response ◽

Network Models ◽

Synaptic Cleft ◽

Receptor Subtypes ◽

Serotonin Level ◽

Adaptive Processes ◽

Response Increase ◽

Ssri Treatment

Selective serotonin reuptake inhibitors (SSRI) are blocking the serotonin transporter and decreasing the re-uptake of serotonin from extracellular space into the neuron. This mechanism increases time-dependently the serotonin level in the extracellular space, e.g. in the synaptic cleft. However, several adaptive processes including receptor subtypes and transporter down- and up-regulation, desensitization of autoreceptors in the raphe nuclei, increase of neurotrophic factors as the BDNF, etc. have been attributed to the therapeutic response. Increase of serotonin in the extracellular space is an inssuficient explanation of treatment effects according to the latency in the therapeutic response and the in- and decrease in gene expression of several hundreds of genes during SSRI treatment. Network models with the involvement of several core players in this neuroplastic process are necessary. The main focus will be within the serotonergic system using promising neuroimaging methods as molecular neuroimaging with PET and functional magnetic resonance imaging.

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Dynamics of biochemical changes in anxious-depressed patients under treatment with antidepressants with different mechanisms of action on serotonin reuptake

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.139 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S119-S120

Author(s):

M. Uzbekov ◽

N. Maximova

Keyword(s):

Serotonin Reuptake ◽

Amine Oxidase ◽

Severity Of Illness ◽

Biochemical Changes ◽

Clinical Severity ◽

Albumin Concentration ◽

Anxious Depression ◽

Group I ◽

Mao Activity ◽

Competing Interest

ObjectivesPharmacodynamics of serotonergic antidepressants differently influencing on serotonin reuptake receptors is poorly investigated.AimTo compare biochemical profiles at patients with anxious depression under treatment with tianeptine–serotonin reuptake enhancer and sertraline–selective serotonin reuptake inhibitor.MethodsPlatelet monoamine oxidase (MAO) and serum amine oxidase (AO) activities, level of middle mass endotoxic molecules (MMEM) and serum albumin functional properties – effective albumin concentration (EAC) and reserve of albumin binding (RAB) were investigated at 43 patients with anxious depression (F 32.1 and F 33.1). Clinical severity of illness was assessed using Hamilton Depression (21 items) and Hamilton Anxiety Scales. All patients were divided in two groups: group I (21 person) received tianeptine (37, 5 mg/day), group II – sertraline (50 mg/day).ResultsIt was established that patients with anxious depression were characterized by significant increase in MAO activity (by 95%) and the level of MMEM (by 86%) and significant decrease in AO activity (by 28%) and EAC and RAB parameters by 43 and 38%, respectively, in comparison with healthy volunteers. Under tianeptine and sertraline treatment, there were revealed contrary directed changes of all investigated parameters.ConclusionResults of study show that both tianeptine and sertraline are equally effective in treatment of anxious depression. Present biochemical investigation, however, suggest that underlying biochemical changes are more complete following tianeptine treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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