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 antagonize α1-adrenergic receptors. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.

Marketed

 * Etoperidone (Axiomin, Etonin)
 * Lorpiprazole (Normarex)
 * Mepiprazole (Psigodal)
 * Nefazodone (Serzone, Nefadar)
 * Trazodone (Desyrel)

Miscellaneous

 * Vilazodone (Viibryd) – a related drug but does not fit into this class as it does not function as a serotonin antagonist, acting solely as a 5-HT1A receptor partial agonist instead.
 * Vortioxetine (Trintellix) – another closely related drug, could technically be considered to be a member of this group, but both vilazodone and vortioxetine are instead generally labeled as serotonin modulators and stimulators.
 * Niaprazine (Nopron) – a drug related to this group but does not inhibit the reuptake of serotonin or the other monoamines.
 * Medifoxamine (Clédial, Gerdaxyl) – could perhaps technically be said to belong to this group, as it is a serotonin–dopamine reuptake inhibitor and 5-HT2A and 5-HT2C receptor antagonist, but not grouped as such.

Never marketed

 * Lubazodone (YM-992, YM-35995) – a SARI that was never marketed.

Binding profiles
The binding profiles of SARIs and some metabolites in terms of their affinities (Ki, nM) for various receptors and transporters are as follows:

These drugs act as antagonists or inverse agonists of the 5-HT2A, α1-adrenergic, and H1 receptors, as partial agonists of the 5-HT1A receptor, and as inhibitors of the transporters. mCPP is an antagonist of the 5-HT2B receptor, an agonist of the 5-HT1A, 5-HT2C, and 5-HT3 receptors, and acts as a partial agonist of the human 5-HT2A and 5-HT2C receptors.