Vernakalant

Structural formula
General
Non-proprietary name	Vernakalant
other names	(3 R ) -1 - [(1 R , 2 R ) -2- [2- (3,4-Dimethoxyphenyl) ethoxy] cyclohexyl] pyrrolidin-3-ol
Molecular formula	C 20 H 31 NO 4 C 20 H 32 NO 4 Cl (Vernakalant hydrochloride )
External identifiers / databases
CAS number 794466-70-9 (Vernakalant) 748810-28-8 ( vernakalant hydrochloride ) EC number 616-691-2 ECHA InfoCard 100.121.790 PubChem 9930049 ChemSpider 8105680 DrugBank DB06217 Wikidata Q665725
Drug information
ATC code	C01 BG11
properties
Molar mass	349.46 g · mol -1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances danger H and P phrases H: 314 P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Vernakalant (trade name BRINAVESS ^® ; manufacturer Cardiome ) is a drug from the group of antiarrhythmics that is used to treat cardiac arrhythmias .

In September 2010 it was approved in the European Union and other countries. In the United States of America, the approval process in the Phase III ACT V study has been paused by the competent authority to clarify any connections with complications.

field of use

Vernakalant is approved for atrial fibrillation or flutter if this is only temporary, i.e. H. less than seven days. It is infused into a vein as a solution over ten minutes. If the heart rhythm fails to normalize, the dose can be repeated in a lower dose after 15 minutes at the earliest.

Mode of action

Vernakalant acts mainly on the atrium of the heart . It extends the atrial refractory period and delays the conduction speed depending on the heart rate. The mechanism of action is based on the one hand on the inhibition of potassium channels in the cell membrane of the heart muscle cells . This reduces the potassium outflow during the action potential ( potassium channel blocker ), so that the action potential lasts longer and the heart rate drops. In addition, potassium channels in the ventricles and sodium channels are also inhibited, which explains undesirable effects such as ventricular fibrillation or a prolonged QT time .

Vernakalant is pharmacotherapeutically assigned to the group "Other antiarrhythmics, class I and class III ". It differs from pure potassium channel blockers in that it has a stronger effect at higher heart rates.

metabolism

Vernakalant is broken down in the liver by cytochrome CYP2D6 and further excretion of the glucuronide by the kidneys. The half-life is three to four hours.

properties

There are potentially eight stereoisomers . The trans isomers are biologically or pharmacologically active, whereas the pharmacological properties of the cis isomers are not known. The hydrochloride salt of vernakalant is used medicinally. Of the possible polymorphic forms, vernakalant hydrochloride is in form A in Brinavess . Vernakalant hydrochloride is very soluble in water.

Individual evidence

1. ↑ There is not yet a harmonized classification for this substance . A labeling of 3-pyrrolidinol, 1 - [(1R, 2R) -2- [2- (3,4-dimethoxyphenyl) ethoxy] cyclohexyl] -, (3R) - in the Classification and Labeling is shown, which is derived from a self-classification by the distributor Inventory of the European Chemicals Agency (ECHA), accessed on August 11, 2016.
2. ↑ Company information  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.  
3. ↑ German Society for Cardiology - Heart and Circulation Research eV: Pocket guidelines for atrial fibrillation , p. 28.
4. ↑ M. Finnin: Vernakalant: A novel agent for the termination of atrial fibrillation. In: American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists. Volume 67, Number 14, July 2010, pp. 1157-1164, doi : 10.2146 / ajhp080501 , PMID 20592320 (review).
5. ↑ Z. Mao, JJ Wheeler, R. Townsend, Y. Gao, S. Kshirsagar, JJ Keirns: Population pharmacokinetic-pharmacodynamic analysis of vernakalant hydrochloride injection (RSD1235) in atrial fibrillation or atrial flutter. In: Journal of pharmacokinetics and pharmacodynamics. Volume 38, Number 5, October 2011, pp. 541-562, doi : 10.1007 / s10928-011-9207-3 , PMID 21786177 .
6. ↑ Assessment Report for Brinavess adopted by the CHMP, European Medicines Agency, September 2010.

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