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-HT_2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also act as α₁-adrenergic receptor antagonists. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.

List of SARIs

• 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-HT_1A receptor partial agonist instead.

Niaprazine is also related to this group but does not inhibit the reuptake of serotonin or the other monoamines.

Medifoxamine could perhaps also be said to belong to this group, as it is a serotonin-dopamine reuptake inhibitor and 5-HT_2A and 5-HT_2C receptor antagonist.

Pharmacology

Binding profile

The affinities (K_d (nM)) of a selection of SARIs have been compared below at an assortment of binding sites:

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-HT_1A where they are partial agonists, and as inhibitors of all transporters listed.

See also

• Serotonin modulator and stimulator (SMS)
• Noradrenergic and specific serotonergic antidepressant (NaSSA)
• Norepinephrine-dopamine disinhibitor (NDDI)
• Selective Serotonin Reuptake Inhibitor (SSRI)