5-HT4 receptor
5-hydroxytryptamine receptor 4 is a protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the HTR4 gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...



The receptor is located in the alimentary tract, urinary bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...

, heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

 and adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

 as well as the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

In the CNS the receptor appears in the putamen
The putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus...

, caudate nucleus
Caudate nucleus
The caudate nucleus is a nucleus located within the basal ganglia of the brains of many animal species. The caudate nucleus is an important part of the brain's learning and memory system.-Anatomy:...

, nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...

, globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...

 and substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...

 and to a lesser extent in the neocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...

, raphe
Raphe nuclei
The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. Their main function is to release serotonin to the rest of the brain...

 and pontine nuclei
Pontine nuclei
The pontine nuclei are a part of the pons involved in motor activity. Corticopontine fibres carry information from the primary motor cortex to the ipsilateral pontine nucleus in the ventral pons, and the pontocerebellar projection then carries that information to the contralateral cerebellum via...

 and some areas of the thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...

It has not been found in the cerebellum.


Several drugs which act as 5-HT4 selective agonists have recently been introduced into use in both scientific research and clinical medicine. Some drugs which act as 5-HT4 agonists are also active as 5-HT3 antagonists, such as mosapride, metoclopramide, renzapride and zacopride, and so these compounds cannot be considered highly selective. Research in this area is ongoing.

SB-207,145 radiolabeled with carbon-11 is used as a radioligand
A radioligand is a radioactive biochemical substance that is used for diagnosis or for research-oriented study of the receptor systems of the body....

 for 5-HT4 in positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

and human


  • BIMU-8
  • Cisapride
    Cisapride is a gastroprokinetic agent, a drug which increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous...

  • CJ-033,466
    CJ-033,466 is a drug which acts as a potent and selective 5-HT4 serotonin receptor partial agonist. In animal tests it stimulated gastrointestinal motility with 30 times the potency of cisapride, and with lower affinity for the hERG channel....

     - partial agonist
  • ML-10302
  • Mosapride
    Mosapride is a gastroprokinetic agent that acts as a selective 5HT4 agonist which accelerates gastric emptying and is used for the treatment of acid reflux, irritable bowel syndrome and functional dyspepsia....

  • Prucalopride
    Prucalopride is a drug acting as a selective, high affinity 5-HT4 receptor agonist which targets the impaired motility associated with chronic constipation, thus normalising bowel movements...

  • Renzapride
    Renzapride is a gastroprokinetic agent and antiemetic which acts as a full 5-HT4 full agonist and 5-HT3 antagonist. It also functions as a 5-HT2B antagonist and has some affinity for the 5-HT2A and 5-HT2C receptors, though it is unlikely that these properties contribute to its therapeutic...

  • RS-67506
  • RS-67333 - partial agonist
  • SL65.0155
    SL65.0155 is a selective 5-HT4 receptor partial agonist . It potently enhances cognition, learning, and memory, and also possesses antidepressant effects...

     - partial agonist
  • Tegaserod
    Tegaserod is a 5-HT4 agonist manufactured by Novartis and sold under the name Zelnorm for the management of irritable bowel syndrome and constipation. Approved by the FDA in 2002, it was subsequently removed from the market in 2007 due to FDA concerns about possible adverse cardiovascular effects...

  • Zacopride
    Zacopride is a potent antagonist at the 5HT3 receptor and an agonist at the 5HT4 receptor. It has anxiolytic and nootropic effects in animal models, with the enantiomer being the more active form...


  • Piboserod
    Piboserod is a selective 5-HT4 receptor antagonist which was marketed and manufactured by GlaxoSmithKline under the trade name Serlipet for the management of atrial fibrillation and irritable bowel syndrome...

  • GR-113,808
    GR-113,808 is a drug which acts as a potent and selective 5-HT4 serotonin receptor antagonist. It is used in researching the roles of 5-HT4 receptors in various processes, and has been used to test some of the proposed therapeutic effects of selective 5-HT4 agonists, such as for instance blocking...

     (1-methyl-1H-indole-3-carboxylic acid, [1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl ester)
  • GR-125,487
  • RS-39604 (1-[4-Amino-5-chloro-2-(3,5-dimethoxyphenyl)methyloxy]-3-[1-[2-methylsulphonylamino]piperidin-4-yl]propan-1-one)
  • SB-203,186
  • SB-204,070
    SB-204,070 is a drug which acts as a potent and selective 5-HT4 serotonin receptor antagonist , and is used for research into the function of this receptor subtype....

  • ([Methoxy-11C]1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate
  • Chamomile (ethanol extract)

Further reading

  • Licht CL, 2009, Changes in the 5-HT4 receptor in animal models of depression and antidepressant treatment, PhD thesis, University of Copenhagen
    University of Copenhagen
    The University of Copenhagen is the oldest and largest university and research institution in Denmark. Founded in 1479, it has more than 37,000 students, the majority of whom are female , and more than 7,000 employees. The university has several campuses located in and around Copenhagen, with the...

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