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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H31NO4
Molecular Weight 349.4644
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VERNAKALANT

SMILES

COC1=CC=C(CCO[C@@H]2CCCC[C@H]2N3CC[C@@H](O)C3)C=C1OC

InChI

InChIKey=VBHQKCBVWWUUKN-KZNAEPCWSA-N
InChI=1S/C20H31NO4/c1-23-19-8-7-15(13-20(19)24-2)10-12-25-18-6-4-3-5-17(18)21-11-9-16(22)14-21/h7-8,13,16-18,22H,3-6,9-12,14H2,1-2H3/t16-,17-,18-/m1/s1

HIDE SMILES / InChI

Molecular Formula C20H31NO4
Molecular Weight 349.4644
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800015306 | http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001215/WC500097150.pdf

Vernakalant is a new antiarrhythmic drug that acts selectively in the atrium, targeting atrial specific channels. Vernakalant is an anti-arrhythmic medicine that acts preferentially in the atria by prolonging atrial refractoriness and by rate-dependently slowing impulse conduction. These anti-fibrillatory actions on refractoriness and conduction are thought to suppress reentry, and are potentiated in the atria during atrial fibrillation. The preferential effects of vernakalant on the atria are postulated to result from its block of currents that are expressed in the atria (e.g., the ultra-rapid delayed rectifier potassium current; and the acetylcholine-activated potassium current), but not in the ventricles, as well as the unique electrophysiologic condition of the fibrillating atria. An oral formulation of vernakalant is in phase II development as a long-term maintenance therapy for patients with atrial fibrillation. An intravenous formulation of vernakalant has been launched in most countries in Europe and Latin America, and in Hong Kong, for the acute conversion of atrial fibrillation. The product has been approved for the acute conversion of atrial fibrillation in South Africa, Iceland, Turkey and is awaiting approval for the same indication in Canada. Phase III development of the IV formulation is ongoing at sites in Asia, and development is currently on hold in the US.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
BRINAVESS

Approved Use

BRINAVESS 20 mg/ml concentrate for solution for infusion (vernakalant hydrochloride) is indicated for rapid conversion of recent onset atrial fibrillation to sinus rhythm in adults

Launch Date

1.28321284E12
PubMed

PubMed

TitleDatePubMed
The effect of vernakalant (RSD1235), an investigational antiarrhythmic agent, on atrial electrophysiology in humans.
2007 Jul
New antiarrhythmic treatment of atrial fibrillation.
2007 Jul
Vernakalant in the management of atrial fibrillation.
2008 Apr
[Amiodaron for treatment of perioperative cardiac arrythmia: a broad spectrum antiarrythmetic agent?].
2008 Dec
The cardiac persistent sodium current: an appealing therapeutic target?
2008 Mar
Vernakalant: pharmacology electrophysiology, safety and efficacy.
2008 May
New antiarrhythmic drugs for atrial fibrillation: focus on dronedarone and vernakalant.
2008 Oct
Kv1.5 blockers for the treatment of atrial fibrillation: approaches to optimization of potency and selectivity and translation to in vivo pharmacology.
2009
Novel approaches for pharmacological management of atrial fibrillation.
2009
Pharmacologic management of atrial fibrillation: established and emerging options.
2009 Aug
Vernakalant hydrochloride for the rapid conversion of atrial fibrillation after cardiac surgery: a randomized, double-blind, placebo-controlled trial.
2009 Dec
Vernakalant hydrochloride for the treatment of atrial fibrillation.
2009 Dec
Atrial-selective pharmacological therapy for atrial fibrillation: hype or hope?
2009 Jan
Recent advances in the pharmacological treatment of cardiac arrythmias.
2009 Nov
Atrial fibrillation: from ion channels to bedside treatment options.
2009 Nov-Dec
New pharmacological agents for arrhythmias.
2009 Oct
Modeling of high-affinity binding of the novel atrial anti-arrhythmic agent, vernakalant, to Kv1.5 channels.
2009 Oct
[New antiarrhythmic drugs for treatment of atrial fibrillation].
2010
[New developments in the antiarrhythmic therapy of atrial fibrillation].
2010 Dec
A multicenter, open-label study of vernakalant for the conversion of atrial fibrillation to sinus rhythm.
2010 Jun
New and emerging antiarrhythmic and anticoagulant agents for atrial fibrillation.
2010 May 1
Usefulness of vernakalant hydrochloride injection for rapid conversion of atrial fibrillation.
2010 Nov 1
Vernakalant, a mixed sodium and potassium ion channel antagonist that blocks K(v)1.5 channels, for the potential treatment of atrial fibrillation.
2010 Sep
Patents

Sample Use Guides

BRINAVESS is dosed by patient body weight, with a maximum calculated dose based upon 113 kg. The recommended initial infusion is 3 mg/kg to be infused over a 10 minute period. For patients weighing ≥ 113 kg, the maximum initial dose of 339 mg (84.7 ml of 4 mg/ml solution) should not exceeded. If conversion to sinus rhythm does not occur within 15 minutes after the end of the initial infusion, a second 10 minute infusion of 2 mg/kg may be administered. For patients weighing ≥ 113 kg, the maximum second infusion of 226 mg (56.5 ml of 4 mg/ml solution) should not exceeded .Cumulative doses of greater than 5 mg/kg should not be administered within 24 hours. Cumulative doses above 565 mg have not been evaluated.
Route of Administration: Intravenous
3-30 μM Vernakalant in canine pulmonary vein sleeve preparations produced small (10-15 ms) increases in action potential duration and suppressed delayed afterdepolarization-mediated triggered activity induced by isoproterenol and high calcium.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:28:39 UTC 2023
Edited
by admin
on Fri Dec 15 15:28:39 UTC 2023
Record UNII
9G468C8B13
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VERNAKALANT
INN   MI   WHO-DD  
INN  
Official Name English
vernakalant [INN]
Common Name English
Vernakalant [WHO-DD]
Common Name English
3-PYRROLIDINOL, 1-((1R,2R)-2-(2-(3,4-DIMETHOXYPHENYL)ETHOXY)CYCLOHEXYL)-, (3R)-
Systematic Name English
VERNAKALANT [MI]
Common Name English
(3R)-1-((1R,2R)-2-(2-(3,4-DIMETHOXYPHENYL)ETHOXY)CYCLOHEXYL)PYRROLIDIN-3-OL
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C47793
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
WHO-ATC C01BG11
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
WHO-VATC QC01BG11
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
NCI_THESAURUS C93038
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
Code System Code Type Description
PUBCHEM
9930049
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
FDA UNII
9G468C8B13
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
INN
8733
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
MESH
C524581
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
WIKIPEDIA
VERNAKALANT
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
EPA CompTox
DTXSID60229659
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
NCI_THESAURUS
C152864
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
CAS
794466-70-9
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
EVMPD
SUB127269
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
DRUG BANK
DB06217
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
ChEMBL
CHEMBL2111112
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
DRUG CENTRAL
4365
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
MERCK INDEX
m11427
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY Merck Index
SMS_ID
100000153301
Created by admin on Fri Dec 15 15:28:39 UTC 2023 , Edited by admin on Fri Dec 15 15:28:39 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY