Ketanserin ( INN,

USAN 280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk（于山國）was Ulleungdo（鬱陵島） Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to th ...

BAN Ban, or BAN, may refer to: Law * Ban (law), a decree that prohibits something, sometimes a form of censorship, being denied from entering or using the place/item ** Imperial ban (''Reichsacht''), a form of outlawry in the medieval Holy Roman ...

) (brand name Sufrexal; former developmental code name R41468) is a

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 inhala ...

used clinically as an

antihypertensive agent Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests th ...

and in

scientific research The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific m ...

to study the

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 va ...

system; specifically, the 5-HT₂ receptor family. It was discovered at

Janssen Pharmaceutica Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American ...

in 1980. It is not available in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

Uses

Medical uses

Ketanserin is classified as an

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests th ...

by the

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...

and the

National Institute of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

. It has been used to reverse pulmonary hypertension caused by

protamine Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in t ...

(which in turn was administered to reverse the effects of

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treat ...

overdose). The reduction in hypertension is not associated with reflex tachycardia. It has been used in cardiac surgery. A 2000

Cochrane Review Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...

found that, compared to placebo, ketanserin did not provide significant relief for people suffering from

Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...

attacks in the setting of

progressive systemic sclerosis Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are two m ...

(an autoimmune disorder). While the frequency of the attacks was unaffected by ketanserin, there was a reduction in the duration of the individual attacks. However, due to the significant adverse effect burden, the authors concluded that ketanserin's utility for this indication is likely unbeneficial. Ketanserin is a selective 5-HT_2A receptor antagonist that was initially developed as an anti-hypertensive medicine. However, now the drug is available as a topical gel formulation for treating wounds, burns, ulcers, and anal fissures. Its action is through the acceleration of epithelialization.

Research uses

With

tritium Tritium ( or , ) or hydrogen-3 (symbol T or H) is a rare and radioactive isotope of hydrogen with half-life about 12 years. The nucleus of tritium (t, sometimes called a ''triton'') contains one proton and two neutrons, whereas the nucleus of ...

(³H) radioactively labeled ketanserin is used as a

radioligand A radioligand is a radioactive biochemical substance (in particular, a ligand (biochemistry), ligand that is radioactive tracer, radiolabeled) that is used for diagnosis or for research-oriented study of the receptor (biochemistry), receptor system ...

for serotonin 5-HT₂ receptors, e.g. in receptor binding assays and

autoradiography An autoradiograph is an image on an X-ray film or nuclear emulsion produced by the pattern of decay emissions (e.g., beta particles or gamma rays) from a distribution of a radioactive substance. Alternatively, the autoradiograph is also available ...

. This radio-labeling has enabled the study of serotonin 5-HT_2A receptor

distribution Distribution may refer to: Mathematics * Distribution (mathematics), generalized functions used to formulate solutions of partial differential equations *Probability distribution, the probability of a particular value or value range of a vari ...

in the

human brain The human brain is the central organ of the human nervous system, and with the spinal cord makes up the central nervous system. The brain consists of the cerebrum, the brainstem and the cerebellum. It controls most of the activities of ...

. An autoradiography study of the human

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebe ...

has found an increasing binding of ³H-ketanserin with age (from below 50 femtomol per milligram tissue at around 30 years of age to over 100 above 75 years). The same research team found no significant correlation with age in their

homogenate Homogeneity and heterogeneity are concepts often used in the sciences and statistics relating to the uniformity of a substance or organism. A material or image that is homogeneous is uniform in composition or character (i.e. color, shape, ...

binding study. Ketanserin has also been used with

carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon ma ...

(¹¹C) radioactively labeled NNC112 in order to image cortical D₁ receptors without contamination by 5-HT₂ receptors. Increasing research into the use of

psychedelics Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science of ...

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 effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...

s has seen ketanserin used to both block the hallucinogenic experience, and to disentangle the specific cognitive effects of 5-HT_2A activation.

Pharmacology

Pharmacodynamics

Ketanserin is a high-affinity non-selective

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, ri ...

of 5-HT₂ receptors in rodents, In addition to the 5-HT₂ receptors, ketanserin is also a high affinity antagonist for the H₁ receptor. It has also been found to block the

vesicular monoamine transporter 2 The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—partic ...

(VMAT2).

Pharmacokinetics

The

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

of ketanserin is 50%. The plasma protein binding of ketanserin is 95.0% and it is mainly bound to

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Album ...

. The

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the b ...

of ketanserin is 10 to 29 hours.

Synthesis

Either 3-(2-Chloroethyl)quinazoline-2,4(1H,3H)-dione 081-87-8(1a), or alternatively 2,3-dihydro- ,3xazolo ,3-buinazolin-5-one 2727-44-3(1b) can be used as starting material. Attachment of the sidechain to 4-(4-Fluorobenzoyl)piperidine 6346-57-7(2) completes synthesis synthesis of Ketanserin (3).

References

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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ...

, titlestyle = background:#ccccff , list1 = {{Adrenergic receptor modulators {{Dopamine receptor modulators {{Histamine receptor modulators {{Monoamine reuptake inhibitors {{Serotonin receptor modulators 5-HT1D antagonists 5-HT2A antagonists 5-HT2C antagonists 5-HT6 antagonists 5-HT7 antagonists Alpha-1 blockers Alpha-2 blockers Antihypertensive agents D1 antagonists D2 antagonists Fluoroarenes H1 receptor antagonists Imides Janssen Pharmaceutica Ketones Piperidines Quinazolinones VMAT inhibitors