Ketanserin

• R- 41468
• 3 - { 2 - [4 - (4- fluorobenzoyl ) piperidin- 1-yl] ethyl} quinazolin- 2, 4 ( 1H, 3H) -dione

C02KD01

Antihypertensives

Template: Infobox chemical / molecular formula search available

Ketanserin is a drug selected from the group of serotonin antagonists, used in the treatment of high blood pressure (hypertension). Ketanserin is not allowed in the German-speaking countries for treatment. In experimental pharmacology ketanserin is in the study of mechanisms of drug application.

• 2.1 Mode of action ( pharmacodynamics )
• 2.2 pharmacokinetics

• 3.1 Therapeutic indications (indications )
• 3.2 contraindications ( contraindications)
• 3.3 Adverse Drug Reactions

Chemistry

Ketanserin is a polycyclic chemical compound that is one of the aromatic ketones, lactams and piperidine derivatives.

Synthesis

For the manufacture of ketanserin various methods, starting from 4 - (4 - fluorobenzoyl ) piperidine described. As a synthesis starting from 2,3-dihydro- 5H -oxazole [2,3 -b] quinazolin- 5-one and 4 - (4 - fluorobenzoyl ) piperidine possible. The condensation of 3 - ( 2-chloroethyl ) -2,4 - (1H, 3H)- quinazolinedione with 4 - ( 4- fluorobenzoyl ) piperidine in the presence of sodium carbonate in 4-methyl -2-pentanone leads to the final product ketanserin. For the production of radiolabelled with 3H or 14C -labeled ketanserin is a multistep process that at a condensation of 4 - (4- fluorobenzoyl ) piperidine with N-(2 -bromoethyl )-2- nitrobenzamide, a reduction with hydrogen, platinum -carbon catalysis and cyclization with urea -based, described. The radioactive isotope is thereby added in the form of hydrogen or urea.

Pharmacology

Mode of action ( pharmacodynamics )

Ketanserin is a moderately selective serotonin antagonist. It has its highest affinity for the serotonin receptor 5-HT2A, he already inhibited at concentrations of about 1 nmol / l. Higher concentrations can also ketanserin other serotonin receptors, particularly 5 -HT2C inhibit.

The blood pressure lowering effect of Ketanserins but brought primarily to inhibition of α1 adrenoceptors of the type in compound ketanserin also blocked at therapeutic doses. Also in histamine receptors of type H1 can ketanserin binding at therapeutic concentrations. Thus, its pharmacological effects on a complex inhibiting serotonin ( normal ) epinephrine and histamine -mediated signal transduction pathways can be recycled.

In higher concentrations ketanserin inhibits additionally among other hERG potassium channels and can therefore lead to a prolongation of the QT interval on the ECG and thus cardiac arrhythmias.

Pharmacokinetics

After its release from an oral dosage form of ketanserin is added to about 50 % in the systemic circulation. In the bloodstream it is 95 % bound to plasma proteins. Ketanserin undergoes extensive metabolism. Its main metabolite is pharmacologically inactive Ketanserinol which is mainly excreted in the urine. The elimination is done with a triphasic kinetics, the terminal plasma half-life is about 14 hours.

Clinical Application

Areas of application (indications )

Ketanserin is an antihypertensive agent ( antihypertensive ). In German-speaking countries it is not approved for this purpose. In other countries, the potential application areas of ketanserin were severely restricted. Therefore, ketanserin is practically used only as a reserve for critical increase in blood pressure, especially during surgery or pregnancy poisoning.

Contraindications ( contraindications)

Due to the possibility of extension of the QT interval on the electrocardiogram ketanserin is in different cardiac arrhythmias, including atrioventricular block second or third degree, bradycardia less than 50 beats per minute, ventricular tachycardia, ventricular fibrillation and sick sinus syndrome, contraindicated. In addition, ketanserin is not be used in known hypersensitivity to this drug and hypokalemia.

Adverse drug reactions

Among the commonly observed under the application of ketanserin side effects include dry mouth, weight gain, dizziness, fatigue, and headache. In clinical trials could also several cases of cardiac arrhythmias, including ventricular tachycardia and torsade de pointes, are observed.

Commercial preparations

Ketanserin is currently in Europe. Merely in the Netherlands under the brand name Ketesin on the market Ketanserinpräparate that were previously in other European countries in the transport, such as Aseranox ( GB), Perketan (I) Serepress (I) and Sufrexal (B, CH, CZ, DK, P, PL, T), are now out of trading.