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Trade names | Sufrexal |
Other names | R41468; R-41468; R-41,468 |
AHFS/Drugs.com | International Drug Names |
Routes of administration | Oral |
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Pharmacokinetic data | |
Bioavailability | 50% [1] [2] |
Protein binding | 95.0% (mainly albumin [2] |
Elimination half-life | 10–29 hours [3] [1] [2] |
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ECHA InfoCard | 100.070.598 |
Chemical and physical data | |
Formula | C22H22FN3O3 |
Molar mass | 395.434 g·mol−1 |
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Ketanserin (INN, USAN, BAN) (brand name Sufrexal; former developmental code name R41468) is a drug used clinically as an antihypertensive agent and in scientific research to study the serotonergic system; specifically, the 5-HT2 receptor family. [4] It was discovered at Janssen Pharmaceutica in 1980. [5] [6] It is not available in the United States. [1]
Ketanserin is classified as an antihypertensive by the World Health Organization [7] and the National Institute of Health. [8]
It has been used to reverse pulmonary hypertension caused by protamine (which in turn was administered to reverse the effects of heparin overdose). [9]
The reduction in hypertension is not associated with reflex tachycardia. [10]
It has been used in cardiac surgery. [11]
A 2000 Cochrane Review found that, compared to placebo, ketanserin did not provide significant relief for people suffering from Raynaud's phenomenon attacks in the setting of progressive systemic sclerosis (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. [12]
Ketanserin is a selective 5-HT2A 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.
With tritium (3H) radioactively labeled ketanserin is used as a radioligand for serotonin 5-HT2 receptors, e.g. in receptor binding assays and autoradiography. [13] This radio-labeling has enabled the study of serotonin 5-HT2A receptor distribution in the human brain. [14]
An autoradiography study of the human cerebellum 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). [15] The same research team found no significant correlation with age in their homogenate binding study.
Ketanserin has also been used with carbon (11C) radioactively labeled NNC112 in order to image cortical D1 receptors without contamination by 5-HT2 receptors. [16]
Increasing research into the use of psychedelics as antidepressants has seen ketanserin used to both block the hallucinogenic experience, and to disentangle the specific cognitive effects of 5-HT2A activation. [17]
Target | Affinity (Ki) | Ref(s) |
---|---|---|
α1A-adrenergic | 6.3 nM | [19] |
α1B-adrenergic | 6.3 nM | [19] |
α1D-adrenergic | 16 nM | [19] |
α2A-adrenergic | 372 nM (HT29) | [18] |
α2B-adrenergic | 199 nM | [18] |
α2C-adrenergic | 159 nM (opossum) | [18] |
5-HT1A | 1,044–>10,000 nM | [19] [18] |
5-HT1B | 2,515–6,300 nM | [19] [18] |
5-HT1D | 32–>10,000 nM | [19] [20] [21] |
5-HT1E | >10,000 nM | [18] |
5-HT1F | 1.25–>10,000 nM | [18] |
5-HT2A | 0.20–9.8 nM | [19] [18] |
5-HT2B | 200–3,236 nM | [19] [18] |
5-HT2C | 17–186 nM | [19] [18] |
5-HT3 | >10,000 nM (rodent) | [18] |
5-HT4L | 1,000 nM (rat) | [18] |
5-HT5A | 20,000 nM | [19] [18] |
5-HT5B | 1,000–1,585 nM (rodent) | [18] |
5-HT6 | 2,800 nM | [18] |
5-HT7 | 320–1,334 nM | [19] [18] |
D1 | 190–464 nM | [18] |
D2 | >10,000 nM | [18] |
D3 | ? | |
D4 | 148 nM (canine) | [18] |
D5 | 2,500 nM | [19] [18] |
H1 | 1.79 nM | [18] |
DAT | >10,000 nM | [18] |
VMAT1 | 1,600 nM | [19] |
VMAT2 | 500 nM | [19] |
Ketanserin is a high-affinity non-selective antagonist of 5-HT2 receptors in rodents, [18] [22] [20] In addition to the 5-HT2 receptors, ketanserin is also a high affinity antagonist for the H1 receptor. [23] It has also been found to block the vesicular monoamine transporter 2 (VMAT2). [24] [25]
The bioavailability of ketanserin is 50%. [1] [2] The plasma protein binding of ketanserin is 95.0% and it is mainly bound to albumin. [2] The elimination half-life of ketanserin is 10 to 29 hours. [3] [1]
Either 3-(2-Chloroethyl)quinazoline-2,4(1H,3H)-dione [5081-87-8] (1a), or alternatively 2,3-dihydro-[1,3]oxazolo[2,3-b]quinazolin-5-one [52727-44-3] (1b) can be used as starting material. Attachment of the sidechain to 4-(4-Fluorobenzoyl)piperidine [56346-57-7] (2) completes synthesis synthesis of Ketanserin (3).
Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors, as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken by mouth or by injection into a vein. The formulation that is taken by mouth comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken by mouth.
Maprotiline, sold under the brand name Ludiomil among others, is a tetracyclic antidepressant (TeCA) that is used in the treatment of depression. It may alternatively be classified as a tricyclic antidepressant (TCA), specifically a secondary amine. In terms of its chemistry and pharmacology, maprotiline is closely related to other secondary amine TCAs like nortriptyline and protriptyline, and has similar effects to them.
Pindolol, sold under the brand name Visken among others, is a nonselective beta blocker which is used in the treatment of hypertension. It is also an antagonist of the serotonin 5-HT1A receptor, preferentially blocking inhibitory 5-HT1A autoreceptors, and has been researched as an add-on therapy to selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression.
Phenoxybenzamine is a non-selective, irreversible alpha blocker.
Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and in the treatment of migraine. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.
Ritanserin, also known by its developmental code name R-55667, is a serotonin antagonist medication described as an anxiolytic, antidepressant, antiparkinsonian agent, and antihypertensive agent. It was chiefly investigated as a drug to treat insomnia, especially to enhance sleep quality by significantly increasing slow wave sleep by virtue of potent and concomitant 5HT2a and 5HT2c antagonism
Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.
The 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 (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations. 5-HT is short for 5-hydroxy-tryptamine or serotonin. 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 as the visual cortex and the orbitofrontal cortex. This receptor was first noted for its importance as a target of serotonergic psychedelic drugs such as LSD and psilocybin mushrooms. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic drugs, especially the atypical ones.
Mianserin, sold under the brand name Tolvon among others, is an atypical antidepressant that is used primarily in the treatment of depression in Europe and elsewhere in the world. It is a tetracyclic antidepressant (TeCA). Mianserin is closely related to mirtazapine, both chemically and in terms of its actions and effects, although there are significant differences between the two drugs.
Pipamperone, also known as carpiperone and floropipamide or fluoropipamide, and as floropipamide hydrochloride (JAN), is a typical antipsychotic of the butyrophenone family used in the treatment of schizophrenia and as a sleep aid for depression. It is or has been marketed under brand names including Dipiperon, Dipiperal, Piperonil, Piperonyl, and Propitan. Pipamperone was discovered at Janssen Pharmaceutica in 1961, and entered clinical trials in the United States in 1963.
The 5-HT3 antagonists, informally known as "setrons", are a class of drugs that act as receptor antagonists at the 5-HT3 receptor, a subtype of serotonin receptor found in terminals of the vagus nerve and in certain areas of the brain. With the notable exceptions of alosetron and cilansetron, which are used in the treatment of irritable bowel syndrome, all 5-HT3 antagonists are antiemetics, used in the prevention and treatment of nausea and vomiting. They are particularly effective in controlling the nausea and vomiting produced by cancer chemotherapy and are considered the gold standard for this purpose.
A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action of serotonin and serotonergic drugs at serotonin (5-HT) receptors.
The serotonin 1A receptor is a subtype of serotonin receptors, or 5-HT receptors, that binds serotonin, also known as 5-HT, a neurotransmitter. 5-HT1A is expressed in the brain, spleen, and neonatal kidney. It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, and its activation in the brain mediates hyperpolarisation and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene.
5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT).
The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) The 5-HT7 receptor is coupled to Gs (stimulates the production of the intracellular signaling molecule cAMP) and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various blood vessels. This receptor has been a drug development target for the treatment of several clinical disorders. The 5-HT7 receptor is encoded by the HTR7 gene, which in humans is transcribed into 3 different splice variants.
WAY-100635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at the D4 receptor. It is sometimes referred to as a silent antagonist at the former receptor. It is closely related to WAY-100135.
Quipazine is a serotonergic drug of the piperazine group which is used in scientific research. It was originally intended as an antidepressant but never developed for medical use.
Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also antagonize α1-adrenergic receptors. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.
Clorotepine, also known as octoclothepin or octoclothepine, is an antipsychotic of the tricyclic group which was derived from perathiepin in 1965 and marketed in the Czech Republic by Spofa in or around 1971 for the treatment of schizophrenic psychosis.
Pirenperone (INN, USAN, BAN; developmental code names R-47456, R-50656) is a serotonin receptor antagonist described as an antipsychotic and tranquilizer which was never marketed. It is a relatively selective antagonist of the serotonin 5-HT2 receptors and has been used in scientific research to study the serotonin system. In the 1980s, the drug was found to block the effects of the lysergic acid diethylamide (LSD) in animals, and along with ketanserin, led to the elucidation of the 5-HT2A receptor as the biological mediator of the effects of serotonergic psychedelics.