Serotonin modulator and stimulator

A serotonin modulator and stimulator (SMS), sometimes referred to more simply as a serotonin modulator, is a type of drug with a multimodal action specific to the serotonin neurotransmitter system. To be precise, SMSs simultaneously modulate one or more serotonin receptors and inhibit the reuptake of serotonin. The term was created to describe the mechanism of action of the serotonergic antidepressant vortioxetine (Brintellix/Trintellix), which acts as a serotonin reuptake inhibitor (SRI), partial agonist of the 5-HT_1A receptor, and antagonist of the 5-HT₃ and 5-HT₇ receptors. However, it can also technically be applied to vilazodone (Viibryd), 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, vomiting, and the gastrointestinal tract – 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.

See also

• Serotonin antagonist and reuptake inhibitor (SARI)
• Selective serotonin reuptake inhibitor (SSRI)
• Noradrenergic and specific serotonergic antidepressant (NaSSA)
• Tricyclic antidepressant (TCAs)