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 Medication 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 19.0 10.5 Venlafaxine 8.9 1060 9300 Vilazodone 1.6 Vortioxetine 5.4 Amitriptyline 4.30 35 3250 Clomipramine 0.28 38 2190 Imipramine 1.40 37 8500
SERT occupancy + occupancy by SRIs at clinically approved dosages Medication Dosage range(mg/day) ~80% occupancy(mg/day) 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 0.67–4 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)
Marketed Citalopram (Celexa) Dapoxetine (Priligy) Escitalopram (Lexapro, Cipralex) Fluoxetine (Prozac) Fluvoxamine (Luvox) Paroxetine (Paxil, Seroxat) Sertraline (Zoloft, Lustral)
Discontinued Indalpine (Upstene) Zimelidine (Normud, Zelmid)
Never marketed Alaproclate (GEA-654) Cericlamine (JO-1017) Desmethylcitalopram Didesmethylcitalopram Femoxetine (FG-4963; Malexil) Ifoxetine (CGP-15,210-G) Omiloxetine Panuramine (WY-26,002) Pirandamine (AY-23,713) RTI-353 Seproxetine ((S)-norfluoxetine)
Dual serotonin reuptake inhibitors and serotonin receptor modulators
Marketed Trazodone (Desyrel) Vilazodone (Viibryd) Vortioxetine (Trintellix)
Never marketed Cianopramine (Ro 11-2465) Litoxetine (SL-810,385) Lubazodone (YM-992, YM-35,995) SB-649,915
Serotonin reuptake inhibition as a weaker/unintended secondary effect
Marketed Dextromethorphan (DXM; Robitussin) Dextropropoxyphene (Darvon) Dimenhydrinate (Dramamine) Diphenhydramine (Benadryl) Mepyramine (pyrilamine) (Anthisan) Mifepristone (Korlym, Mifeprex)
Never marketed 4′-Fluorococaine (also a Dopamine reuptake inhibitor) Delucemine (also an NMDA antagonist) Mesembrenone (also a weak PDE4 inhibitor (found in Sceletium tortuosum (kanna)) Mesembrine (also a weak PDE4 inhibitor (found in Sceletium tortuosum (kanna))Pharmaceutical compositions containing mesembrine and related compounds. U.S. Patent 6,288,104 (PDF) Roxindole (EMD-49,980) (also a 5-HT1A and D2-like receptor agonist)
See also Dopamine reuptake inhibitor Monoamine reuptake inhibitor SNTX-2643
References