Serotonin antagonist and reuptake inhibitors (SARIs) are a class 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 ...

s used mainly as

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, but also as anxiolytics and

hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...

s. They act by antagonizing

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neur ...

s such as 5-HT_2A and inhibiting the reuptake of

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 ...

, norepinephrine, and/or

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 ...

. Additionally, most also antagonize α₁-adrenergic receptors. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.

List of SARIs

Marketed

Etoperidone Etoperidone, associated with several brand names, is an atypical antidepressant which was developed in the 1970s and either is no longer marketed or was never marketed. It is a phenylpiperazine related to trazodone and nefazodone in chemical str ...

(Axiomin, Etonin) *

Lorpiprazole Lorpiprazole (INN) (brand name Normarex) is a marketed anxiolytic drug of the phenylpiperazine group. It has been described as a serotonin antagonist and reuptake inhibitor (SARI) in the same group as trazodone, nefazodone, and etoperidone. S ...

(Normarex) *

Mepiprazole Mepiprazole (INN, BAN) (brand name Psigodal) is an anxiolytic drug of the phenylpiperazine group with additional antidepressant properties that is marketed in Spain. It acts as a 5-HT2A and α1-adrenergic receptor antagonist and inhibits th ...

(Psigodal) * Nefazodone (Serzone, Nefadar) * Trazodone (Desyrel)

Miscellaneous

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) – a related drug but does not fit into this class as it does not function as a serotonin antagonist, acting solely as a 5-HT_1A receptor partial agonist instead. *

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) – 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 A serotonin modulator and stimulator (SMS), sometimes referred to more simply as a serotonin modulator, is a type of drug with a multimodal action specific to the serotonin neurotransmitter system. To be precise, SMSs simultaneously modulate one or ...

. *

Niaprazine Niaprazine ( INN) (brand name Nopron) is a sedative-hypnotic drug of the phenylpiperazine group. It has been used in the treatment of sleep disturbances since the early 1970s in several European countries including France, Italy, and Luxembourg. ...

(Nopron) – a drug related to this group but does not inhibit the reuptake of serotonin or the other monoamines. *

Medifoxamine Medifoxamine, previously sold under the brand names Clédial and Gerdaxyl, is an atypical antidepressant with additional anxiolytic properties acting via dopaminergic and serotonergic mechanisms which was formerly marketed in France and Spain, as ...

(Clédial, Gerdaxyl) – could perhaps technically be said to belong to this group, as it is a

serotonin–dopamine reuptake inhibitor A serotonin–dopamine reuptake inhibitor (SDRI) is a type of drug which acts as a reuptake inhibitor of the monoamine neurotransmitters serotonin and dopamine by blocking the actions of the serotonin transporter (SERT) and dopamine transport ...

and 5-HT_2A and 5-HT_2C receptor

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

, but not grouped as such.

Never marketed

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-35995) – a SARI that was never marketed.

Pharmacology

Binding profiles

The binding profiles of SARIs and some

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s in terms of their

affinities In post-classical history, an affinity was a collective name for the group ( retinue) of (usually) men whom a lord gathered around himself in his service; it has been described by one modern historian as "the servants, retainers, and other foll ...

(, ) for various

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

s and

transporter Transporter may refer to: * Transporter (vehicles), types of vehicles designed to transport items * Transporter wagon, a railway car designed to carry another railway car * Volkswagen Transporter, a model of van * Transporter bridge, a bridge wh ...

s are as follows: These drugs act as

antagonists An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

s of the 5-HT_2A, α₁-adrenergic, and H₁ receptors, as partial agonists of the 5-HT_1A receptor, and as

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

s of the transporters. mCPP is an antagonist of the 5-HT_2B receptor, an agonist of the 5-HT_1A, 5-HT_2C, and 5-HT₃ receptors, and acts as a partial agonist of the human 5-HT_2A and 5-HT_2C receptors.

References

{{Monoamine reuptake inhibitors Antidepressants Anxiolytics Serotonin receptor antagonists Serotonin reuptake inhibitors