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.

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-HT1A 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-HT2A and 5-HT2C 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:

+ Compound 5-HT1A 5-HT2A 5-HT2B 5-HT2C 5-HT3 5-HT6 5-HT7 α1 α2 D2 H1 Etoperidone 890 20,000 52,000 85 36 38 570 2,300 3,100 >35,000 Hydroxynefazodone 165–1,203 376–1,053 56–589 7.2–34 8.0–145 63–2,490 11,357 202–432 1,940–4,360 44–400 32–398 3.2–63 3.4–251 427 1,748 163 97–2,900 106–570 >10,000 326 >10,000 Nefazodone 200–459 360–618 360 80 26 72 5.5–48 84–640 910 ≥370 >10,000 Trazodone 160–367 ≥8,500 ≥7,400 96–118 20–45 74–189 224–402 >10,000 >10,000 1,782 12–153 106–728 ≥3,500 220–1,100 >10,000 Triazoledione ≥34,527 >100,000 636–1,371 159–211 173 1,915 >100,000 Values are (). The smaller the value, the more strongly the drug binds to the site. For assay species and references, see the individual drug articles. Most but not all values are for human proteins.

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.

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) DSP-6745

References