NIFEKALANT HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H27N5O5.ClH
Molecular Weight	441.909
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CN1C(=O)C=C(NCCN(CCO)CCCC2=CC=C(C=C2)[N+]([O-])=O)N(C)C1=O

InChI

InChIKey=YPVGGQKNWAKOPX-UHFFFAOYSA-N

InChI=1S/C19H27N5O5.ClH/c1-21-17(14-18(26)22(2)19(21)27)20-9-11-23(12-13-25)10-3-4-15-5-7-16(8-6-15)24(28)29;/h5-8,14,20,25H,3-4,9-13H2,1-2H3;1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21772943
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/16157956

Nifekalant is a class III antiarrhythmic agent approved in Japan for the treatment of arrhythmias and ventricular tachycardia. It has the brand name Shinbit. It is a nonselective K+ channel blocker without any β-blocking actions. Administration of nifekalant suppressed sustained ventricular tachyarrhythmias in acute coronary syndrome patients, and in cardiac arrest victims as well as during or after cardiac surgery. The major adverse effect of nifekalant is QT interval prolongation and occurrence of torsades de pointes which requires frequent monitoring of the QT interval during nifekalant infusion with adequate dose adjustment.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Multidrug and toxin extrusion protein 2 2 Target ID: CHEMBL1743127 Sources: http://www.ncbi.nlm.nih.gov/pubmed/23241029	Inhibitor 8297		2.7 µM [IC50]
HERG 92 Target ID: CHEMBL240 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12460639	Inhibitor 8297		7.9 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Arrhythmia 38 Sources: http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=485522	Primary		Approved 8429	Shinbit Approved Use For the treatment of arrhythmia Launch Date 1999

PubMed

Title	Date	PubMed
[Synthesis and vasorelaxant activities of benzopyran-4-one hydrazone derivatives].	2002 Aug	12567776
Pretreatments with a novel pure potassium channel blocker, Nifekalant, were effective in the electrical atrial defibrillation: a report of two cases.	2002 Dec	12797359
Inhibitory effect of the class III antiarrhythmic drug nifekalant on HERG channels: mode of action.	2002 Dec 13	12460639
[Recent findings on the dromotropic actions of the class III antiarrhythmic agents].	2002 Nov	12491809
Effect of nifekalant on acute electrical remodelling in rapid atrial pacing canine model.	2006 Dec 20	17199956
Drug therapy for ventricular tachyarrhythmia in heart failure.	2007	17587746
Mutational analysis of block and facilitation of HERG current by a class III anti-arrhythmic agent, nifekalant.	2007 May-Jun	18690032
Characterization of transient atrial rhythm occurring between typical atrial flutter and its termination with class III drugs.	2008 Aug	18684249
Human atrial natriuretic peptide suppresses torsades de pointes in rabbits.	2008 May	18441465
Effects of intravenous nifekalant as a lifesaving drug for severe ventricular tachyarrhythmias complicating acute coronary syndrome.	2009 Nov	19724153
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003

Patents

Sample Use Guides

In Vivo Use Guide

For acute coronary syndrome treatment the mean dose level of nifekalant was 0.19 ± 0.14 mg/kg body weight per hour; For peri-operative Ventricular tachyarrhythmia treatment - intravenous administration of nifekalant in a dose of 0.3 mg/kg; For cardiopulmonary resuscitation treatment - 0.15-0.3 mg/kg followed by intravenous infusion of 0.3-0.4 mg/kg per hour as antiarrhythmic therapy

Route of Administration: Intravenous

In Vitro Use Guide

Nifekalant in concentrations of 1 and 10 uM prolonged the action potential durations of Purkinje fiber and the free wall in a concentration-dependent manner in dogs.

Name

Type

Language

NIFEKALANT HYDROCHLORIDE

Common Name

English

NIFEKALANT HYDROCHLORIDE [MI]

Common Name

English

Nifekalant hydrochloride [WHO-DD]

Common Name

English

Code System Code Type Description

SMS_ID

100000086472