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, which acts as a serotonin reuptake inhibitor (SRI), agonist of the 5-HT1A receptor, and antagonist of the 5-HT3 and 5-HT7 receptors. However, it can also technically be applied to vilazodone, which is an antidepressant as well and acts as an SRI and 5-HT1A 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-HT1A 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-HT1A 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.

It is similar to the marketing strategy used for the drug brexpiprazole, labeling it as a "serotonin-dopamine activity modulator" or 'SDAM'.