Serotonin antagonist and reuptake inhibitor

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

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

Binding profile

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

References

  1. ↑ 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.
  2. 1 2 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.
  3. 1 2 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.
  4. 1 2 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.
  5. 1 2 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.
  6. ↑ 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.
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