Selective serotonin reuptake enhancer

A selective serotonin reuptake enhancer (SSRE) is a type of drug

Drug

A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

which enhances the plasmalemmal reuptake

Reuptake

Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....

of the neurotransmitter

Neurotransmitter

Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

serotonin

Serotonin

Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, leading to a decrease in its synaptic

Synaptic

Synaptic may refer to:*Synapse, part of the nervous system*Synapsis, the pairing of two homologous chromosomes*Synaptic , a Linux graphical package management program for APT See also...

concentration

Concentration

In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

s and therefore a decrease in serotonergic

Serotonergic

Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...

neurotransmission

Neurotransmission

Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...

.

The only known drug of this class is tianeptine

Tianeptine

Tianeptine was discovered by The French Society of Medical Research in the 1960s. Under the trade-names it is a drug used for treating major depressive episodes ....

(Stablon, Coaxil, Tatinol), which is structurally related to the tricyclic antidepressant

Tricyclic antidepressant

Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...

s 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

AMPA receptor

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog 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.

SSREs are used as antidepressant

Antidepressant

An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

s for the treatment of depression

Clinical depression

Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...

and anxiety

Anxiety

Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, and are in marked contrast to other antidepressants such as the selective serotonin reuptake inhibitor

Selective serotonin reuptake inhibitor

Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...

s (SSRIs), which inhibit

Reuptake inhibitor

A reuptake inhibitor , also known as a transporter blocker, is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore an...

the reuptake of serotonin instead. 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, although interestingly, it has also been shown that the SSRI fluoxetine

Fluoxetine

Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...

can substitute for tianeptine in animal studies.

Although several related compounds are disclosed in the original patent, it is unclear whether these share tianeptine's unique pharmacological effects. Amineptine

Amineptine

Amineptine was developed by the French Society of Medical research in the 1960s. Under the trade-names is used as an atypical tricyclic antidepressant that selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting...

, the most closely related drug to have been widely studied, is a dopamine reuptake inhibitor

Dopamine reuptake inhibitor

A dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...

with no significant effect on serotonin levels (conversely, tianeptine has no affinity for the dopamine transporter).