Serotonin antagonist and reuptake inhibitor
Introduction Chemical structure of the serotonin antagonist and reuptake inhibitor trazodone. '''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===* 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.
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)
References