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-HT_2A 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.

List of SARIs

Marketed

Commercially available serotonin antagonist and reuptake inhibitors include etoperidone (Axiomin, Etonin), lorpiprazole (Normarex), mepiprazole (Psigodal), nefazodone, utility complicated by life-threatening idiosyncratic hepatotoxicity (Serzone, Nefadar), and trazodone (Desyrel).

Never marketed

• lubazodone (YM-992, YM-35995) – a SARI that, as of this date, had not come to market.

Miscellaneous

• vilazodone (Viibryd) – a related drug not fitting into this class, as it acts solely as a 5-HT_1A receptor partial agonist, but not as a serotonin antagonist; generally labeled as serotonin modulator and stimulator.
• vortioxetine (Trintellix) – another closely related drug generally labeled as a serotonin modulator and stimulator.
• niaprazine (Nopron) – a related drug that does not inhibit the reuptake of serotonin or other monoamines.
• medifoxamine (Clédial, Gerdaxyl) – a serotonin–dopamine reuptake inhibitor and 5-HT_2A and 5-HT_2C receptor antagonist, although not grouped as such.

Pharmacology

Binding profiles

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

These drugs act as antagonists or inverse agonists of the 5-HT_2A, α₁-adrenergic, and H₁ receptors, as partial agonists of the 5-HT_1A receptor, and as inhibitors of the transporters. mCPP is an antagonist of the 5-HT_2B receptor, an agonist of the 5-HT_1A, 5-HT_2C, and 5-HT₃ receptors, and acts as a partial agonist of the human 5-HT_2A and 5-HT_2C receptors.

See also

• List of antidepressants
• Serotonin modulator and stimulator (SMS)
• Noradrenergic and specific serotonergic antidepressant (NaSSA)
• Norepinephrine-dopamine disinhibitor (NDDI)
• Selective serotonin reuptake inhibitor (SSRI)

References