Serotonin antagonist and reuptake inhibitor
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Serotonin antagonist and reuptake inhibitors (SARIs) are a class of
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.[1]
Never marketed
- Lubazodone (YM-992, YM-35995) – a SARI that was never marketed.
Pharmacology
Binding profiles
The binding profiles of SARIs and some
Compound | SERT | NET | DAT | 5-HT1A | 5-HT2A | 5-HT2B | 5-HT2C | 5-HT3 | 5-HT6 | 5-HT7 | α1 | α2 | D2 |
H1 |
mACh | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Etoperidone | 890 | 20,000 | 52,000 | 85 | 36 | ND | ND | ND | ND | ND | 38 | 570 | 2,300 | 3,100 | >35,000 | |
Hydroxynefazodone | 165–1,203 | 376–1,053 | ND | 56–589 | 7.2–34 | ND | ND | ND | ND | ND | 8.0–145 | 63–2,490 | ND | ND | 11,357 | |
mCPP | 202–432 | 1,940–4,360 | ND | 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 | ND | 72 | ND | ND | ND | 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 | ND | 636–1,371 | 159–211 | ND | ND | ND | ND | ND | 173 | 1,915 | ND | ND | >100,000 | |
Values are Ki (nM). 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
inhibitors of the transporters. mCPP is an antagonist of the 5-HT2B receptor, an agonist of the 5-HT1A,[3] 5-HT2C, and 5-HT3 receptors,[4][5] and acts as a partial agonist of the human 5-HT2A[6] and 5-HT2C receptors.[7]
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
- S2CID 6978939.
- ^ Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 11 September 2017.
- ^ S2CID 27389008.
- S2CID 20150858.
- PMID 8856697.
- PMID 7965773. Retrieved 2022-10-02.
- PMID 10498829.