Serotonin antagonist and reuptake inhibitor

Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drug

Drug

A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

s used mainly as antidepressant

Antidepressant

An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

s, but also as anxiolytic

Anxiolytic

An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...

s and hypnotic

Hypnotic

Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...

s. They act by antagonizing

Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

serotonin receptors such as 5-HT_2A

5-HT2A receptor

The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...

and inhibiting

Reuptake inhibitor

A reuptake inhibitor , also known as a transporter blocker, is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore an...

the reuptake

Reuptake

Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....

of serotonin

Serotonin

Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, norepinephrine

Norepinephrine

Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

, and/or dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

. Additionally, most also act as α₁-adrenergic receptor

Alpha-1 adrenergic receptor

The alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic...

antagonists

Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

. The majority of the currently marketed SARIs belong to the phenylpiperazine

Phenylpiperazine

1-Phenylpiperazine is a simple chemical compound featuring a phenyl group bound to a piperazine ring. The suffix '-piprazole' is sometimes used in the names of drugs to indicate they belong to this class....

class of compounds.

List of SARIs

Etoperidone
Etoperidone
Etoperidone , also known as clopradone and thozalinone, is an antidepressant of the phenylpiperazine class which was introduced in Europe in 1977...

(Axiomin, Etonin)
Lorpiprazole
Lorpiprazole
Lorpiprazole is an anxiolytic drug of the phenylpiperazine class. It may produce TFMPP as an active metabolite....

(Normarex)
Mepiprazole
Mepiprazole
Mepiprazole is a minor tranquilizer with a phenylpiperazine structure used in Spain for the treatment of anxiety neuroses. It acts as a 5-HT2A and α1-adrenergic receptor antagonist, and has also been shown to inhibit the reuptake and induce the release of serotonin, dopamine, and norepinephrine to...

(Psigodal)
Nefazodone
Nefazodone
Nefazodone is an antidepressant marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries due to the rare incidence of hepatotoxicity , which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in every...

(Serzone, Nefadar)
Trazodone
Trazodone
Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound...

(Desyrel)

Vilazodone

Vilazodone is an SSRI antidepressant developed by Clinical Data for the treatment of major depressive disorder. The chemical compound was originally developed by Merck KGaA ....

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

Partial agonist

Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...

instead.

Niaprazine

Niaprazine

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

is also related to this group but does not inhibit the reuptake of serotonin or the other monoamines, so it does not fit either.

Binding profile

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

Binding site

In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...

s:
| Compound >

SERT Serotonin transporter The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...	NET Norepinephrine transporter The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....	DAT Dopamine transporter The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...	5-HT_1A 5-HT1A receptor The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...	5-HT_2A 5-HT2A receptor The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...	α₁ Alpha-1 adrenergic receptor The alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic...	α₂ Alpha-2 adrenergic receptor The alpha-2 adrenergic receptor is a G protein-coupled receptor associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well...	D₂	H₁ H1 receptor The H1 receptor is a histamine receptor belonging to the family of Rhodopsin like G-protein-coupled receptors. This receptor, which is activated by the biogenic amine histamine, is expressed throughout the body, to be specific, in smooth muscles, on vascular endothelial cells, in the heart, and in...	mACh Muscarinic acetylcholine receptor Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells... >- \| Etoperidone Etoperidone Etoperidone , also known as clopradone and thozalinone, is an antidepressant of the phenylpiperazine class which was introduced in Europe in 1977...	890	20,000	52,000	85	36	38	570	2,300	3,100	35,000 >- \| Nefazodone Nefazodone Nefazodone is an antidepressant marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries due to the rare incidence of hepatotoxicity , which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in every...	200	360	360	80	26	48	640	910	24,000	>- \| Trazodone Trazodone Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound...	160	8,500	7,400	78	16	39	405	3,650	725	>-

The selected ligands act as antagonist

Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

s (or inverse agonist

Inverse agonist

In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....

s depending on the site in question) at all receptor

Receptor (biochemistry)

In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

s listed except at 5-HT_1A where they are partial agonist

Partial agonist

Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...

s, and as inhibitor

Reuptake inhibitor

s of all transporters listed.

List of SARIs

Binding profile

See also