A serotonin reuptake inhibitor (SRI) is a type of

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

which acts as a

reuptake inhibitor Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transmi ...

of the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

(5-hydroxytryptamine, or 5-HT) by blocking the

action Action may refer to: * Action (narrative), a literary mode * Action fiction, a type of genre fiction * Action game, a genre of video game Film * Action film, a genre of film * ''Action'' (1921 film), a film by John Ford * ''Action'' (1980 fil ...

of the

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...

(SERT). This in turn leads to increased

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', ''molar concentration'', ''number concentration'', an ...

s of serotonin and, therefore, an increase in

serotonergic Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...

. It is a type of

monoamine reuptake inhibitor A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine ...

(MRI); other types of MRIs include

dopamine reuptake inhibitor A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopa ...

s and

norepinephrine reuptake inhibitor A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epineph ...

s. SRIs are not synonymous with

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...

s (SSRIs), as the latter term is usually used to describe the

class Class or The Class may refer to: Common uses not otherwise categorized * Class (biology), a taxonomic rank * Class (knowledge representation), a collection of individuals or objects * Class (philosophy), an analytical concept used differentl ...

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

s of the same name, and because SRIs, unlike SSRIs, can either be selective or non-selective in their

. For example,

cocaine Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...

, which non-selectively inhibits the reuptake of

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

, and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

, is an SRI but not an SSRI. SRIs are used predominantly as

s (e.g., SSRIs, SNRIs, and TCAs), though they are also commonly used in the treatment of other psychological conditions such as

anxiety disorder Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...

s and

eating disorder An eating disorder is a mental disorder defined by abnormal eating behaviors that negatively affect a person's physical or mental health. Only one eating disorder can be diagnosed at a given time. Types of eating disorders include binge eating d ...

s. Less often, SRIs are also used to treat a variety of other

medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medica ...

s including

neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...

and

fibromyalgia Fibromyalgia (FM) is a medical condition defined by the presence of chronic widespread pain, fatigue, waking unrefreshed, cognitive symptoms, lower abdominal pain or cramps, and depression. Other symptoms include insomnia and a general hyp ...

(e.g.,

duloxetine Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth. It is a serotoni ...

milnacipran Milnacipran (trade names Ixel, Savella, Dalcipran, Toledomin) is a serotonin–norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia. It is not approved for the clinical treatment of major depressive disorder in ...

), and

premature ejaculation Premature ejaculation (PE) occurs when a man expels semen (and most likely experiences orgasm) soon after beginning sexual activity, and with minimal penile stimulation. It has also been called ''early ejaculation'', ''rapid ejaculation'', ''r ...

(e.g.,

dapoxetine Dapoxetine, marketed as Priligy, among others, is a medication used for the treatment of premature ejaculation (PE) in men 18–64 years old. Dapoxetine works by inhibiting the serotonin transporter, increasing serotonin's action at the postsyna ...

) as well as for dieting (e.g.,

sibutramine Sibutramine, formerly sold under the brand name Meridia among others, is an appetite suppressant which has been discontinued in many countries. It works as a serotonin–norepinephrine reuptake inhibitor similar to a tricyclic antidepressant. Un ...

). Additionally, some clinically used drugs such as

chlorpheniramine Chlorphenamine (CP, CPM), also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis (hay fever). It is taken by mouth. The medication takes effect within two hours and las ...

dextromethorphan Dextromethorphan (DXM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. In 2022, the FDA approved a formulation of it combined with bu ...

, and

methadone Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...

possess SRI properties secondarily to their primary

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...

(s) and this contributes to their

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

and

drug interaction Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug, ...

profiles. A closely related type of drug is a

serotonin releasing agent A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter e ...

(SRA), an example of which is

fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome.https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212102s003lb ...

Comparison of SRIs

Binding profiles

SERT occupancy

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 transporter Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs (SERT, DAT, NET) are responsible fo ...

s (MATs) are listed below. For a list of SRIs that act at multiple MATs, see other

pages such as SNRI and SNDRI.

Selective serotonin reuptake inhibitors (SSRIs)

Marketed

Citalopram Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and socia ...

(Celexa) *

Dapoxetine Dapoxetine, marketed as Priligy, among others, is a medication used for the treatment of premature ejaculation (PE) in men 18–64 years old. Dapoxetine works by inhibiting the serotonin transporter, increasing serotonin's action at the postsyna ...

(Priligy) *

Escitalopram Escitalopram, sold under the brand names Lexapro and Cipralex, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. Escitalopram is mainly used to treat major depressive disorder and generalized anxiet ...

(Lexapro, Cipralex) * Fluoxetine (Prozac) *

Fluvoxamine Fluvoxamine, sold under the brand name Luvox and Faverin among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and obsessive–compulsive disorder ...

(Luvox) *

Paroxetine Paroxetine, sold under the brand names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder ...

(Paxil, Seroxat) *

Sertraline Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The efficacy of sertraline for depression is similar to that of other antidepressants, and the differ ...

(Zoloft, Lustral)

Discontinued

Indalpine Indalpine (INN, BAN; brand name Upstène; developmental code name LM-5008) is a selective serotonin reuptake inhibitor (SSRI) class drug that was briefly marketed. It was discovered in 1977 by the pharmacologists Le Fur and Uzan at Pharmuka, a s ...

(Upstene) *

Zimelidine Zimelidine (INN, BAN) (brand names Zimeldine, Normud, Zelmid) was one of the first selective serotonin reuptake inhibitor (SSRI) antidepressants to be marketed. It is a pyridylallylamine, and is structurally different from other antidepressants ...

(Normud, Zelmid)

Never marketed

Alaproclate Alaproclate (developmental code name GEA-654) is a drug that was being developed as an antidepressant by the Swedish pharmaceutical company Astra AB (now AstraZeneca) in the 1970s. It acts as a selective serotonin reuptake inhibitor (SSRI), and ...

(GEA-654) *

Cericlamine Cericlamine (INN; developmental code JO-1017) is a potent and moderately selective serotonin reuptake inhibitor (SSRI) of the amphetamine family (specifically, a derivative of phentermine, and closely related to chlorphentermine, a highly selecti ...

(JO-1017) *

Desmethylcitalopram Desmethylcitalopram is an active metabolite of the antidepressant drugs citalopram (racemic) and escitalopram (the ''S''-enantiomer, which would be called desmethylescitalopram). Like citalopram and escitalopram, desmethylcitalopram functions as ...

Didesmethylcitalopram Didesmethylcitalopram is an active metabolite of the antidepressant drug citalopram (racemic). Didesmethyl''es''citalopram is an active metabolite of the antidepressant escitalopram, the ''S''-enantiomer of citalopram. Like citalopram and escital ...

Femoxetine Femoxetine (INN; tentative brand name Malexil; developmental code name FG-4963) is a drug related to paroxetine that was being developed as an antidepressant by Danish pharmaceutical company Ferrosan in 1975 before acquisition of the company by ...

(FG-4963; Malexil) *

Ifoxetine Ifoxetine (CGP-15,210-G) is a selective serotonin reuptake inhibitor (SSRI) which was investigated as an antidepressant in the 1980s but was never marketed. Ifoxetine selectively blocks the reuptake of serotonin in the brain supposedly without ...

(CGP-15,210-G) *

Omiloxetine Omiloxetine (omiloextinum, omiloxetino INN) was a selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive diso ...

Panuramine Panuramine (Wy-26,002) is an antidepressant which was synthesized in 1981 by Wyeth. It acts as a potent and selective serotonin reuptake inhibitor (SSRI). It was never marketed. See also * Selective serotonin reuptake inhibitor Selecti ...

(WY-26,002) *

Pirandamine Pirandamine (AY-23,713) is a tricyclic derivative which acts as a selective serotonin reuptake inhibitor (SSRI). It was investigated in the 1970s as a potential antidepressant but clinical development was not commenced and it was never marketed. ...

(AY-23,713) *

RTI-353 RTI(-''4229'')-353 is a phenyltropane derived drug which acts as an SSRI. Tamagnan et al. also made some phenyltropanes with high activity and selectivity for the SERT (pM affinity). See also *RTI-83 *Troparil *Tropine *Tropinone Tropinone i ...

Seproxetine Seproxetine, also known as (''S'')-norfluoxetine, is a selective serotonin reuptake inhibitor (SSRI). It is the ''S'' enantiomer of norfluoxetine, the main active metabolite of the widely used antidepressant fluoxetine; but little is known ...

((''S'')-norfluoxetine)

Dual serotonin reuptake inhibitors and serotonin receptor modulators

Marketed

Trazodone Trazodone, sold under many brand names, is an antidepressant medication. It is used to treat major depressive disorder, anxiety disorders, and difficulties with sleep. The medication is taken orally. Common side-effects include dry mouth, f ...

(Desyrel) *

Vilazodone Vilazodone, sold under the brand name Viibryd among others, is a medication used to treat major depressive disorder. It is taken by mouth. Common side effects include nausea, diarrhea, and trouble sleeping. Serious side effects may include in ...

(Viibryd) *

Vortioxetine Vortioxetine, sold under the brand names Trintellix and Brintellix among others, is a medication used to treat major depressive disorder. Effectiveness is viewed as similar to that of other antidepressants. It is taken by mouth. Common side e ...

(Trintellix)

Never marketed

* Cianopramine (Ro 11-2465) *

Litoxetine Litoxetine (developmental code names SL 81-0385, IXA-001) is an antidepressant which was under clinical development for the treatment of major depression, depression in the early 1990s but was never marketed. It acts as a potency (pharmacology), ...

(SL-810,385) *

Lubazodone Lubazodone (developmental code names YM-992, YM-35995) is an experimental antidepressant which was under development by Yamanouchi for the treatment for major depressive disorder in the late 1990s and early 2000s but was never marketed. It acts ...

(YM-992, YM-35,995) *

SB-649,915 SB-649,915 is a serotonin reuptake inhibitor and 5-HT1A and 5-HT1B receptor antagonist which is being investigated for its antidepressant effects. Relative to the selective serotonin reuptake inhibitors (SSRIs), SB-649,915 has a faster onset ...

Serotonin reuptake inhibition as a weaker/unintended secondary effect

Marketed

Dextromethorphan Dextromethorphan (DXM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. In 2022, the FDA approved a formulation of it combined with bu ...

(DXM; Robitussin) *

Dextropropoxyphene Dextropropoxyphene is an analgesic in the opioid category, patented in 1955 and manufactured by Eli Lilly and Company. It is an optical isomer of levopropoxyphene. It is intended to treat mild pain and also has antitussive (cough suppressant) ...

(Darvon) *

Dimenhydrinate Dimenhydrinate, sold under the brand name Dramamine, among others, is an over-the-counter drug used to treat motion sickness and nausea. Dimenhydrinate is a theoclate salt composed of diphenhydramine, an ethanolamine derivative, and 8-chloroth ...

(Dramamine) *

Diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into a vein ...

(Benadryl) * Mepyramine (pyrilamine) (Anthisan) *

Mifepristone Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion during pregnancy and manage early miscarriage. This combination is 97% effective during the first 63 days of p ...

(Korlym, Mifeprex)

Never marketed

* Delucemine (also an

NMDA antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...

) *

Mesembrenone Mesembrenone is an alkaloid constituent of ''Sceletium tortuosum'' (Kanna) and minor constituent of Lampranthus aureus and Lampranthus spectabilis Similar to modern synthetic antidepressants, it is a potent (IC50 < 1 μM) selective inhibitor ...

(also a weak

PDE4 inhibitor A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of PDE inhibitor ...

(found in ''

Sceletium tortuosum Sceletium tortuosum is a succulent plant commonly found in South Africa, which is also known as Kanna, Channa, Kougoed (Kauwgoed/ 'kougoed', prepared from 'fermenting' ''S. tortuosum'')—which literally means, 'chew(able) things' or 'something ...

'' (kanna)) *

Mesembrine Mesembrine is an alkaloid present in ''Sceletium tortuosum'' (kanna). It has been shown to act as a serotonin reuptake inhibitor (Ki = 1.4 nM), and more recently, has also been found to behave as a weak inhibitor of the enzyme phosp ...

(also a weak

(found in ''

'' (kanna))Pharmaceutical compositions containing mesembrine and related compounds
U.S. Patent 6,288,104(PDF)
/ref> *

Roxindole Roxindole (EMD-49,980) is a dopaminergic and serotonergic drug which was originally developed by Merck KGaA for the treatment of schizophrenia. In clinical trials its antipsychotic efficacy was only modest but it was unexpectedly found to produc ...

(EMD-49,980) (also a 5-HT_1A and D₂-like receptor

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

)

References

{{DEFAULTSORT:Serotonin Reuptake Inhibitor Drugs acting on the nervous system