A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission. It is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.

SRIs are not synonymous with selective serotonin reuptake inhibitors (SSRIs), as the latter term is usually used to describe the class of antidepressants of the same name, and because SRIs, unlike SSRIs, can either be selective or non-selective in their action. For example, cocaine, which non-selectively inhibits the reuptake of serotonin, norepinephrine, and dopamine, is an SRI but not an SSRI.

SRIs are used predominantly as antidepressants (e.g., SSRIs, SNRIs, and TCAs), though they are also commonly used in the treatment of other psychological conditions such as anxiety disorders and eating disorders. Less often, SRIs are also used to treat a variety of other medical conditions including neuropathic pain and fibromyalgia (e.g., duloxetine, milnacipran), and premature ejaculation (e.g., dapoxetine) as well as for dieting (e.g., sibutramine). Additionally, some clinically used drugs such as chlorpheniramine, dextromethorphan, and methadone possess SRI properties secondarily to their primary mechanism of action(s) and this contributes to their side effect and drug interaction profiles.

A closely related type of drug is a serotonin releasing agent (SRA), an example of which is fenfluramine.

Comparison of SRIs

Binding profiles

Binding affinities of SRIs at MATs[1][2]
Medication SERTTooltip Serotonin transporter NETTooltip Norepinephrine transporter DATTooltip Dopamine transporter
Citalopram 1.16 4070 28100
Desmethylcitalopram 3.6 1820 18300
Escitalopram 1.1 7841 27410
Femoxetine 11.0 760 2050
Fluoxetine 0.81 240 3600
Fluvoxamine 2.2 1300 9200
Norfluoxetine 1.47 1426 420
Paroxetine 0.13 40 490
Sertraline 0.29 420 25
Desmethylsertraline 3.0 390 129
Zimelidine 152 9400 11700
Levomilnacipran[3] 19.0 10.5 ND
Venlafaxine 8.9 1060 9300
Vilazodone[3] 1.6 ND ND
Vortioxetine[3] 5.4 ND ND
Amitriptyline 4.30 35 3250
Clomipramine 0.28 38 2190
Imipramine 1.40 37 8500

SERT occupancy

SERT occupancy by SRIs at clinically approved dosages
Medication Dosage range
~80% SERT
Ratio (dosage /
80% occupancy)
Citalopram 20–40 40 0.5–1
Escitalopram 10–20 10 1–2
Fluoxetine 20–80 20 1–4
Fluvoxamine 50–350 70 0.71–5
Paroxetine 10–60 20 0.5–3
Sertraline 25–200 50 0.5–4
Duloxetine 20–120 30 0.67–2
Venlafaxine 75–375 75 1–5
Clomipramine 50–250 10 5–25

List of SERT-selective SRIs

Many SRIs exist, an assortment of which are listed below. Note that only SRIs selective for the SERT over the other monoamine transporters (MATs) are listed below. For a list of SRIs that act at multiple MATs, see other monoamine reuptake inhibitor pages such as SNRI and SNDRI.

Selective serotonin reuptake inhibitors (SSRIs)



Never marketed

Dual serotonin reuptake inhibitors and serotonin receptor modulators


Never marketed

Serotonin reuptake inhibition as a weaker/unintended secondary effect


Never marketed

See also


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