VERNAKALANT

Possibly Marketed Outside US

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 Search

SMILES

COC1=C(OC)C=C(CCO[C@@H]2CCCC[C@H]2N3CC[C@@H](O)C3)C=C1

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21135602
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Voltage-gated potassium channel subunit Kv1.5 43 Target ID: CHEMBL4306 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16302909 \| https://www.ncbi.nlm.nih.gov/pubmed/17872968	Blocker 555	13.0 µM [IC50]
Potassium voltage-gated channel subfamily D member 2 15 Target ID: CHEMBL5885 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16302909	Blocker 555	38.0 µM [IC50]
Voltage-gated potassium channel subunit Kv4.3 7 Target ID: CHEMBL1964 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16302909	Blocker 555	30.0 µM [IC50]
HERG 99 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16302909	Blocker 555	21.0 µM [IC50]
Sodium channel protein type V alpha subunit 49 Target ID: CHEMBL1980 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16302909	Blocker 555	9.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Atrial fibrillation 131 Sources: https://www.medicines.org.uk/emc/PIL.32083.latest.pdf	Primary		Approved 8583	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

C_max

Value	Dose	Analyte	Population
0.083 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.145 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.316 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg single, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.715 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.14 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.04 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	4 mg/kg single, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.85 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.19 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	4 mg/kg single, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.307 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg single, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.87 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg 1 times / hour multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.86 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg 1 times / hour multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.81 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg 1 times / hour multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.71 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg 1 times / hour multiple, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.84 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg 1 times / hour multiple, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.98 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.96 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	3 mg/kg 1 times / hour multiple, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.25 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.25 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.81 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	3 mg/kg 1 times / hour multiple, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
0.171 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.351 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.686 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg single, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.48 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.05 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	4 mg/kg single, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.98 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	4 mg/kg single, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg single, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.37 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg 1 times / hour multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.44 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg 1 times / hour multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.88 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg 1 times / hour multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.29 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.53 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.69 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg 1 times / hour multiple, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10.24 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg 1 times / hour multiple, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.09 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.58 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	3 mg/kg 1 times / hour multiple, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.52 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.52 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.08 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	3 mg/kg 1 times / hour multiple, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg single, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	4 mg/kg single, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	4 mg/kg single, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg single, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg 1 times / hour multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg 1 times / hour multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	0.5 mg/kg 1 times / hour multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg 1 times / hour multiple, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18927241/	2 mg/kg 1 times / hour multiple, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	VERNAKALANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
37% REVIEW https://journals.sagepub.com/doi/full/10.4137/CMT.S1079			VERNAKALANT plasma	Homo sapiens

Doses

Dose	Population	Adverse events
3 mg/kg single, intravenous Studied dose Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/21029824/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21029824/	Disc. AE: Bradycardia, Hypotension... AEs leading to discontinuation/dose reduction: Bradycardia (1.4%) Hypotension (0.7%) Dizziness (0.7%) Urticaria (0.7%) Tachycardia NOS (0.7%) Consciousness loss (0.7%) Ventricular tachycardia (0.7%) Seizure (0.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/21029824/
3 mg/kg single, intravenous Studied dose Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/27233239/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27233239/	Disc. AE: Nausea, Headache... Other AEs: Dysgeusia, Sneezing... AEs leading to discontinuation/dose reduction: Nausea (0.8%) Headache (0.8%) Confusion (0.8%) Cold sweat (0.8%) Sinus arrest (0.8%) Cardiogenic shock (0.8%) Other AEs: Dysgeusia (14.7%) Sneezing (7.8%) Paraesthesia (6.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/27233239/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Nav1.5 116	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9930049#section=BioAssay-Results Page: 2.0	inconclusive [IC50 21.3174 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9930049#section=BioAssay-Results Page: 10.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9930049#section=BioAssay-Results Page: 2.0	yes [IC50 10.684 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18927241/	major		unlikely (pharmacogenomic study) Comment: In the subset that received 2 vernakalant infusions, there was little difference in vernakalant maximum plasma concentration or area under the plasma concentration-time curve from the start of the first infusion to 90 minutes between CYP2D6 poor metabolizers and extensive metabolizers or between those who did or did not receive concomitant CYP2D6-inhibitor medications. Sources: https://pubmed.ncbi.nlm.nih.gov/18927241/
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9930049#section=BioAssay-Results Page: 8.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Nav1.5 119	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxOTgwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxMDczODMifX0=
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjEwNzM4MyJ9fQ==

PubMed

Title	Date	PubMed
The molecular basis of high-affinity binding of the antiarrhythmic compound vernakalant (RSD1235) to Kv1.5 channels.	2007 Dec	17872968
Anti-arrhythmic drug therapy for atrial fibrillation: current anti-arrhythmic drugs, investigational agents, and innovative approaches.	2008 Jun	18515286
New horizons in antiarrhythmic therapy: will novel agents overcome current deficits?	2008 Sep 22	18790110
Kv1.5 blockers for the treatment of atrial fibrillation: approaches to optimization of potency and selectivity and translation to in vivo pharmacology.	2009	19519460
Novel approaches for pharmacological management of atrial fibrillation.	2009	19441867
Recent advances in pharmacotherapy of atrial fibrillation.	2009 Aug	20523864
Atrial-selective pharmacological therapy for atrial fibrillation: hype or hope?	2009 Jan	19077816
[New antiarrhythmic drugs for treatment of atrial fibrillation].	2010	21086684
[Ionic mechanisms of action of class III antiarrhythmic drugs].	2010	20659045
Advances in the treatment of atrial fibrillation.	2010 Dec	21135805
Vernakalant.	2010 Dec	21119728
[New developments in the antiarrhythmic therapy of atrial fibrillation].	2010 Dec	21107985
Beta1-adrenoceptor polymorphism predicts flecainide action in patients with atrial fibrillation.	2010 Jul 2	20625396
Vernakalant hydrochloride: A novel atrial-selective agent for the cardioversion of recent-onset atrial fibrillation in the emergency department.	2010 Nov	21175515
Usefulness of vernakalant hydrochloride injection for rapid conversion of atrial fibrillation.	2010 Nov 1	21029824
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	20730700

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Mon Mar 31 17:58:25 GMT 2025` Edited by `admin` on `Mon Mar 31 17:58:25 GMT 2025`
Record UNII	9G468C8B13
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VERNAKALANT [MI]

Preferred Name

English

VERNAKALANT

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

(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