U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H31NO4.ClH
Molecular Weight 385.925
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VERNAKALANT HYDROCHLORIDE

SMILES

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

InChI

InChIKey=JMHYCBFEEFHTMK-IIUXMCBISA-N
InChI=1S/C20H31NO4.ClH/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;1H/t16-,17-,18-;/m1./s1

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

2010
PubMed

PubMed

TitleDatePubMed
Vernakalant: RSD 1235, RSD-1235, RSD1235.
2007
Vernakalant (RSD1235): a novel, atrial-selective antifibrillatory agent.
2007 Apr
The molecular basis of high-affinity binding of the antiarrhythmic compound vernakalant (RSD1235) to Kv1.5 channels.
2007 Dec
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
Anti-arrhythmic drug therapy for atrial fibrillation: current anti-arrhythmic drugs, investigational agents, and innovative approaches.
2008 Jun
The cardiac persistent sodium current: an appealing therapeutic target?
2008 Mar
Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3, randomized, placebo-controlled trial.
2008 Mar 25
Vernakalant--a promising therapy for conversion of recent-onset atrial fibrillation.
2008 May
Vernakalant (RSD1235) in the management of atrial fibrillation: a review of pharmacological properties, clinical efficacy and safety.
2008 Nov
Mechanisms of atrial fibrillation termination by rapidly unbinding Na+ channel blockers: insights from mathematical models and experimental correlates.
2008 Oct
New antiarrhythmic drugs for atrial fibrillation: focus on dronedarone and vernakalant.
2008 Oct
New horizons in antiarrhythmic therapy: will novel agents overcome current deficits?
2008 Sep 22
Kv1.5 blockers for the treatment of atrial fibrillation: approaches to optimization of potency and selectivity and translation to in vivo pharmacology.
2009
Recent advances in pharmacotherapy of atrial fibrillation.
2009 Aug
Pharmacologic management of atrial fibrillation: established and emerging options.
2009 Aug
Cardioversion for atrial fibrillation: treatment options and advances.
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
Pharmacokinetics of novel atrial-selective antiarrhythmic agent vernakalant hydrochloride injection (RSD1235): influence of CYP2D6 expression and other factors.
2009 Jan
Atrial fibrillation: from ion channels to bedside treatment options.
2009 Nov-Dec
New and emerging antiarrhythmic drugs for atrial fibrillation: what may become available to the clinician in the near future.
2009 Oct
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
Advances in the treatment of atrial fibrillation.
2010 Dec
Vernakalant.
2010 Dec
[New developments in the antiarrhythmic therapy of atrial fibrillation].
2010 Dec
Atrial Ca2+ signaling in atrial fibrillation as an antiarrhythmic drug target.
2010 Mar
Vernakalant hydrochloride: A novel atrial-selective agent for the cardioversion of recent-onset atrial fibrillation in the emergency department.
2010 Nov
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 15:56:45 GMT 2023
Edited
by admin
on Fri Dec 15 15:56:45 GMT 2023
Record UNII
7G4J1ZD9UQ
Record Status Validated (UNII)
Record Version
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Name Type Language
VERNAKALANT HYDROCHLORIDE
DASH   EMA EPAR   MART.   MI   USAN   WHO-DD  
USAN  
Official Name English
VERNAKALANT HYDROCHLORIDE [USAN]
Common Name English
Vernakalant hydrochloride [WHO-DD]
Common Name English
(3R)-1-[(1R,2R)-2-[2-(3,4-dimethoxyphenyl)ethoxy]cyclohexyl]pyrrolidin-3-ol hydrochloride
Systematic Name English
VERNAKALANT HYDROCHLORIDE [MART.]
Common Name English
VERNAKALANT HYDROCHLORIDE [EMA EPAR]
Common Name English
VERNAKALANT HCL
Common Name English
RSD-1235
Code English
KYNAPID
Brand Name English
VERNAKALANT HYDROCHLORIDE [MI]
Common Name English
BRINAVESS
Brand Name English
RSD1235
Code English
Classification Tree Code System Code
NCI_THESAURUS C47793
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
EMA ASSESSMENT REPORTS BRINAVESS (AUTHORIZED: ATRIAL FIBRILLATION)
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
NCI_THESAURUS C93038
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
Code System Code Type Description
CAS
748810-28-8
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
PRIMARY
SMS_ID
100000115500
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
PRIMARY
DRUG BANK
DBSALT002376
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
PRIMARY
FDA UNII
7G4J1ZD9UQ
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
PRIMARY
MERCK INDEX
m11427
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
PRIMARY Merck Index
NCI_THESAURUS
C152865
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
PRIMARY
EVMPD
SUB30707
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
PRIMARY
PUBCHEM
9930048
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
PRIMARY
USAN
RR-36
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
PRIMARY
ChEMBL
CHEMBL2111112
Created by admin on Fri Dec 15 15:56:45 GMT 2023 , Edited by admin on Fri Dec 15 15:56:45 GMT 2023
PRIMARY
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