Serotonin antagonist and reuptake inhibitor



Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also act as α1-adrenergic receptor antagonists. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.

List of SARIs

 * Etoperidone (Axiomin, Etonin)
 * Lorpiprazole (Normarex)
 * Lubazodone (YM-992, YM-35995)
 * Mepiprazole (Psigodal)
 * Nefazodone (Serzone, Nefadar)
 * Trazodone (Desyrel)

Vilazodone is a related drug but does not fit into this class as it does not function as a serotonin antagonist, acting as a 5-HT1A receptor partial agonist instead.

Niaprazine is also related to this group but does not inhibit the reuptake of serotonin or the other monoamines.

Binding profile
The affinities (Kd (nM)) of a selection of SARIs have been compared below at an assortment of binding sites:

The selected ligands act as antagonists (or inverse agonists depending on the site in question) at all receptors listed except at 5-HT1A where they are partial agonists, and as inhibitors of all transporters listed.