Serotonin antagonist and reuptake inhibitor
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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[edit]
- Etoperidone (Axiomin, Etonin)
- Lorpiprazole (Normarex)
- Lubazodone (YM-992, YM-35995)
- Mepiprazole (Psigodal)
- Nefazodone (Serzone, Nefadar)
- Trazodone (Desyrel)
Vilazodone is a related drug but does not fit into this class as it does not function as a serotonin antagonist, acting as a 5-HT1A receptor partial agonist instead. Vortioxetine, 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 is a drug related to this group but does not inhibit the reuptake of serotonin or the other monoamines.
Medifoxamine could technically be said to belong to this group, as it is a serotonin-dopamine reuptake inhibitor and 5-HT2A and 5-HT2C receptor antagonist.[1]
Pharmacology[edit]
Binding profile[edit]
The affinities (Kd (nM)) of a selection of SARIs have been compared below at an assortment of binding sites:[2][3][4][5]
Compound | SERT | NET | DAT | 5-HT1A | 5-HT2A | α1 | α2 | D2 | H1 | mACh |
Etoperidone | 890 | 20,000 | 52,000 | 85 | 36 | 38 | 570 | 2,300 | 3,100 | >35,000 |
Nefazodone | 200 | 360 | 360 | 80 | 26 | 48 | 640 | 910 | 24,000 | 11,000 |
Trazodone | 160 | 8,500 | 7,400 | 78 | 16 | 39 | 405 | 3,650 | 725 | 324,000 |
The selected ligands act as antagonists (or inverse agonists depending on the site in question) at all receptors listed except at 5-HT1A where they are partial agonists,[6] and as inhibitors of all transporters listed.[2][3][4][5]
See also[edit]
- Serotonin modulator and stimulator (SMS)
- Noradrenergic and specific serotonergic antidepressant (NaSSA)
- Norepinephrine-dopamine disinhibitor (NDDI)
- Selective Serotonin Reuptake Inhibitor (SSRI)
References[edit]
- ^ Gainsborough N, Nelson ML, Maskrey V, Swift CG, Jackson SH (1994). "The pharmacokinetics and pharmacodynamics of medifoxamine after oral administration in healthy elderly volunteers". Eur. J. Clin. Pharmacol. 46 (2): 163–6. doi:10.1007/bf00199882. PMID 8039537.
- ^ a b Tatsumi M; Groshan K; Blakely RD; Richelson E (December 1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". European Journal of Pharmacology. 340 (2–3): 249–58. doi:10.1016/S0014-2999(97)01393-9. PMID 9537821.
- ^ a b Wander TJ; Nelson A; Okazaki H; Richelson E (December 1986). "Antagonism by antidepressants of serotonin S1 and S2 receptors of normal human brain in vitro". European Journal of Pharmacology. 132 (2–3): 115–21. doi:10.1016/0014-2999(86)90596-0. PMID 3816971.
- ^ a b Richelson E; Nelson A (July 1984). "Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro". The Journal of Pharmacology and Experimental Therapeutics. 230 (1): 94–102. PMID 6086881.
- ^ a b Cusack B; Nelson A; Richelson E (May 1994). "Binding of antidepressants to human brain receptors: focus on newer generation compounds". Psychopharmacology. 114 (4): 559–65. doi:10.1007/BF02244985. PMID 7855217.
- ^ Odagaki Y; Toyoshima R; Yamauchi T (May 2005). "Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTPgammaS binding". Journal of Psychopharmacology (Oxford, England). 19 (3): 235–41. doi:10.1177/0269881105051526. PMID 15888508.