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Selective Serotonin Reuptake Enhancer

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Selective Serotonin Reuptake Enhancer


A selective serotonin reuptake enhancer (SSRE) is a type of drug which enhances the plasmalemmal reuptake of the neurotransmitter serotonin, leading to a decrease in its synaptic concentrations and therefore a decrease in serotonergic neurotransmission.[1]

The only known drug of this class is tianeptine (Stablon, Coaxil, Tatinol), which is structurally related to the tricyclic antidepressants yet has an entirely distinct mechanism of action. The precise mechanism of action of tianeptine remains unclear despite several decades of research and clinical use, and while it has been speculated that tianeptine might act as an allosteric modulator of the serotonin transporter at a separate site to that used by SSRIs, newer research suggests that its direct action is actually alteration of AMPA glutamate receptor activity, which then leads to enhanced serotonin reuptake via a downstream mechanism which has yet to be fully characterised, but seems to involve altered neuroplasticity and release of BDNF.[2][3][4][5][6][7][8][9]

SSREs are used as antidepressants for the treatment of depression and anxiety, and are in marked contrast to other antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), which inhibit the reuptake of serotonin instead.[1][10] SSREs have been demonstrated to be as effective as SSRIs against depression, have a much faster onset of action (immediate), and have a much better tolerability profile,[1][10] although interestingly, it has also been shown that the SSRI fluoxetine can substitute for tianeptine in animal studies.[11]

Although several related compounds are disclosed in the original patent,[12] it is unclear whether these share tianeptine's unique pharmacological effects. Amineptine, the most closely related drug to have been widely studied, is a dopamine reuptake inhibitor with no significant effect on serotonin levels (conversely, tianeptine has no affinity for the dopamine transporter).

See also

References

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