Recent Advances in Patient Treatment and Care (Track)




Antidepressant tianeptine action is connected with serotonin turnover acceleration in the synapse

Marat G. Uzbekov
Department of Brain Pathology Research Institute of Psychiatry Poteshnaya 3, 107076 Moscow Russia

Abstract:

Antidepressant tianeptine (TIA) is a serotonin (5-hydroxytryptamine) reuptake enhancer. In spite of a numerous trials the neurochemical mechanism of TIA action is not clear.

Aim. All these prompt us to carry out the comparative clinical-biochemical investigation of patients with anxious depression under TIA and sertraline treatment and on the basis of results of the study develop possible mechanism of TIA action (Uzbekov et al., 2006; Uzbekov, 2009).

Results. Twofold increase of platelet monoamine oxidase (MAO) activity in depressed patients indirectly supports the view that anxious depression is characterized by the decrease of serotonergic activity (Kasper, 2001).

Discussion. The problem of TIA action can be solved only from the point of view of structural-functional unity of the synapse. Synapse has to be considered as a complex biological system (nerve\9nerve ending + astrocytes and microlgia) but not as a structure with “reuptake receptor”.

It is supposed that at normal conditions about 75 % of serotonin released in the synaptic cleft undergoes functional inactivation by its reuptake in presynaptic ending. The remaining serotonin (approximately 25 %) is taken up by astroglia and microglia and undergoes there its irreversible (chemical) inactivation (Hughes, 1972; Avakjan, 1976; Whittaker et al., 1983).

According to our hypothesis TIA enhancing serotonin reuptake decreases serotonin level in synaptic cleft. Simultaneously with this process in patients-responders to the treatment we have established that a very high MAO activity starts to decrease. Under TIA action two processes take place in synaptic region – (a) enhancing of serotonin reuptake in nerve ending and (b) inhibition of MAO activity. In a whole we can assume that serotonin concentration in synaptic cleft appeared to be dropped because process (a) is more active then process (b). It has been shown that TIA activates serotonin release from presynaptic ending (Fattachini et al., 1990; 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 the increase in the unit of time serotonin concentration on postsynaptic receptors. This process is accompanied by decrease of MAO activity.

Conclusion. The first time in the literature we propose the hypothesis about neurochemical mechanism of TIA action. According to it TIA activates both serotonin reuptake from and serotonin release in synaptic cleft thus accelerating its turnover in synapse. Proposed mechanism mainly refers to the first acute phase of TIA action directed on the normalization of serotonergic neurotransmission.