A serotonin modulator and stimulator (SMS), sometimes referred to more simply as a serotonin modulator, is a type of

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhala ...

with a multimodal action specific to the

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...

system. To be precise, SMSs simultaneously modulate one or more

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory ne ...

s and inhibit the

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the Synapse, pre-synaptic neuron at a synapse) or glial cell after it has performed its function of ...

of serotonin. The term was created to describe the

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targ ...

of the serotonergic

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...

vortioxetine, which acts as a

serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the action of the serotonin transporter (SERT). This in turn leads to incre ...

(SRI),

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...

of the 5-HT_1A receptor, and

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

of the 5-HT₃ and 5-HT₇ receptors. However, it can also technically be applied to

vilazodone Vilazodone, sold under the brand name Viibryd among others, is a medication used to treat major depressive disorder. It is taken Oral administration, by mouth. Common side effects include nausea, diarrhea, and trouble sleeping. Serious side ef ...

, which is an antidepressant as well and acts as an SRI and 5-HT_1A receptor partial agonist. SMSs were developed because there are many different subtypes of serotonin receptors (at least 15 in total are currently known) and not all of these receptors appear to be involved in the antidepressant effects of SRIs. Some serotonin receptors seem to play a relatively neutral or insignificant role in the regulation of mood, but others, such as 5-HT_1A autoreceptors and 5-HT₇ receptors, appear to play an oppositional role in the efficacy of SRIs in treating depression. As such, a drug which combines the actions of, say, an SRI, 5-HT_1A partial agonism, and 5-HT₇ receptor antagonism, could, in theory, have the potential to prove more effective than pure SRIs. Alternatively, antagonism of 5-HT₃ – a receptor that is involved in the regulation of

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...

, and the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

– could counteract the undesirable increase in activation of this receptor mediated by SRIs, thereby potentially improving tolerability. An alternative term is serotonin partial agonist/reuptake inhibitor (SPARI), which can be applied only to vilazodone. It is similar to the marketing strategy used for the drug

brexpiprazole Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic. It is a dopamine D2 receptor partial agonist and has been described as a "serotonin–dopamine activity modulator" (SDAM). The drug was approved by the ...

, labeling it as a "serotonin-dopamine activity modulator" or 'SDAM'.

References

{{Monoamine reuptake inhibitors Antidepressants Serotonin receptor antagonists Serotonin receptor agonists Serotonin reuptake inhibitors

See also

References