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'.
^Muntner, Stephen M. Stahl ; with illustrations by Nancy (2013). Stahl's essential psychopharmacology : neuroscientific basis and practical application (4th ed.). Cambridge: Cambridge University Press. ISBN978-1107686465.
^Yoshimi, Noriko; Fujita, Yuko; Ohgi, Yuta; Futamura, Takashi; Kikuchi, Tetsuro; Hashimoto, Kenji (2014). "Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors". Pharmacology Biochemistry and Behavior. 124: 245–249. doi:10.1016/j.pbb.2014.06.008. ISSN1873-5177. PMID24955861.