Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C19H27N5O5 |
| Molecular Weight | 405.4482 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1C(=O)C=C(NCCN(CCO)CCCC2=CC=C(C=C2)[N+]([O-])=O)N(C)C1=O
InChI
InChIKey=OEBPANQZQGQPHF-UHFFFAOYSA-N
InChI=1S/C19H27N5O5/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
DescriptionCurator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/16157956
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
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.943 mg/L CLINICAL TRIAL doi:10.1016/j.jchromb.2013.09.003 |
0.6 mg/kg/h 1 times / hour steady-state, intravenous dose: 0.6 mg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
230.95 ng/mL CLINICAL TRIAL https://www.aidic.it/cet/15/46/230.pdf |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
358.62 ng/mL CLINICAL TRIAL https://www.aidic.it/cet/15/46/230.pdf |
0.4 mg/kg single, intravenous dose: 0.4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
444.3 ng/mL CLINICAL TRIAL https://www.aidic.it/cet/15/46/230.pdf |
0.4 mg/kg/h steady-state, intravenous dose: 0.4 mg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4.616 mg × h/L CLINICAL TRIAL doi:10.1016/j.jchromb.2013.09.003 |
0.6 mg/kg/h 1 times / hour steady-state, intravenous dose: 0.6 mg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
209.9 ng × h/mL CLINICAL TRIAL https://www.aidic.it/cet/15/46/230.pdf |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
302.44 ng × h/mL CLINICAL TRIAL https://www.aidic.it/cet/15/46/230.pdf |
0.4 mg/kg single, intravenous dose: 0.4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2627.33 ng × h/mL CLINICAL TRIAL https://www.aidic.it/cet/15/46/230.pdf |
0.4 mg/kg/h steady-state, intravenous dose: 0.4 mg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.3 h CLINICAL TRIAL doi:10.1016/j.jchromb.2013.09.003 |
0.6 mg/kg/h 1 times / hour steady-state, intravenous dose: 0.6 mg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.54 h CLINICAL TRIAL https://www.aidic.it/cet/15/46/230.pdf |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.34 h CLINICAL TRIAL https://www.aidic.it/cet/15/46/230.pdf |
0.4 mg/kg single, intravenous dose: 0.4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.35 h CLINICAL TRIAL https://www.aidic.it/cet/15/46/230.pdf |
0.4 mg/kg/h steady-state, intravenous dose: 0.4 mg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
NIFEKALANT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
0.5 mg/kg single, intravenous Highest studied dose Dose: 0.5 mg/kg Route: intravenous Route: single Dose: 0.5 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Other AEs: Ventricular fibrillation, Torsades de pointes... Other AEs: Ventricular fibrillation (11%) Sources: Torsades de pointes (11%) Premature ventricular contractionson (15%) Non-sustained ventricular tarchycardia (15%) Hypotension (1%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Hypotension | 1% | 0.5 mg/kg single, intravenous Highest studied dose Dose: 0.5 mg/kg Route: intravenous Route: single Dose: 0.5 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Torsades de pointes | 11% | 0.5 mg/kg single, intravenous Highest studied dose Dose: 0.5 mg/kg Route: intravenous Route: single Dose: 0.5 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Ventricular fibrillation | 11% | 0.5 mg/kg single, intravenous Highest studied dose Dose: 0.5 mg/kg Route: intravenous Route: single Dose: 0.5 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Non-sustained ventricular tarchycardia | 15% | 0.5 mg/kg single, intravenous Highest studied dose Dose: 0.5 mg/kg Route: intravenous Route: single Dose: 0.5 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Premature ventricular contractionson | 15% | 0.5 mg/kg single, intravenous Highest studied dose Dose: 0.5 mg/kg Route: intravenous Route: single Dose: 0.5 mg/kg Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| A mechanism underlying compound-induced voltage shift in the current activation of hERG by antiarrhythmic agents. | 2011-11-11 |
|
| Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011-07-14 |
|
| [Successful use of intravenous amiodarone for refractory ventricular fibrillation just after releasing aortic cross-clamp]. | 2010-10 |
|
| Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest. | 2010-08 |
|
| Junctional ectopic tachycardia. | 2010-07-20 |
|
| Effects of landiolol, an ultra-short-acting beta1-selective blocker, on electrical storm refractory to class III antiarrhythmic drugs. | 2010-05 |
|
| Comparative study of nifekalant versus amiodarone for shock-resistant ventricular fibrillation in out-of-hospital cardiopulmonary arrest patients. | 2010-04 |
|
| Nifekalant versus lidocaine for in-hospital shock-resistant ventricular fibrillation or tachycardia. | 2010-01 |
|
| Effects of intravenous nifekalant as a lifesaving drug for severe ventricular tachyarrhythmias complicating acute coronary syndrome. | 2009-11 |
|
| Nifekalant and disopyramide in a patient with short QT syndrome: evaluation of pharmacological effects and electrophysiological properties. | 2008-09 |
|
| Mutational analysis of block and facilitation of HERG current by a class III anti-arrhythmic agent, nifekalant. | 2008-08-12 |
|
| Characterization of transient atrial rhythm occurring between typical atrial flutter and its termination with class III drugs. | 2008-08 |
|
| Human atrial natriuretic peptide suppresses torsades de pointes in rabbits. | 2008-05 |
|
| Clinical study of the acute effects of intravenous nifekalant on the defibrillation threshold in patients with persistent and paroxysmal atrial fibrillation. | 2008-01 |
|
| [Despite medication, overdrive pacing is required to stabilize the electrical storm associated with acute coronary syndrome: a case report]. | 2007-10 |
|
| Effect of nifekalant for acute conversion of atrial flutter: the possible termination mechanism of typical atrial flutter. | 2007-10 |
|
| Analysis of arrhythmogenic profile in a canine model of chronic atrioventricular block by comparing in vitro effects of the class III antiarrhythmic drug nifekalant on the ventricular action potential indices between normal heart and atrioventricular block heart. | 2007-02 |
|
| Mechanisms of destabilization and early termination of spiral wave reentry in the ventricle by a class III antiarrhythmic agent, nifekalant. | 2007-01 |
|
| Is the combination therapy of IKr-channel blocker and left stellate ganglion block effective for intractable ventricular arrhythmia in a cardiopulmonary arrest patient? | 2007 |
|
| Drug therapy for ventricular tachyarrhythmia in heart failure. | 2007 |
|
| Effect of nifekalant on acute electrical remodelling in rapid atrial pacing canine model. | 2006-12-20 |
|
| Reduced inotropic effect of nifekalant in failing hearts in rats. | 2006-09 |
|
| Effects of antiarrhythmic drugs on apoptotic pathways in H9c2 cardiac cells. | 2006-08 |
|
| Comparison of efficacy of sotalol and nifekalant for ventricular tachyarrhythmias. | 2006-05 |
|
| Molecular determinants of HERG channel block. | 2006-05 |
|
| [Strategy for cardiac arrhythmias in acute coronary syndrome]. | 2006-04 |
|
| Comparison of nifekalant and lidocaine for the treatment of shock-refractory ventricular fibrillation. | 2006-04 |
|
| Destabilization and early termination of spiral-wave reentry by a class III antiarrhythmic agent, nifekalant, in a perfused two-dimensional layer of rabbit ventricular myocardium. | 2006-02-17 |
|
| Fatal case of amiodarone-induced acute respiratory distress syndrome in a patient with severe left ventricular dysfunction due to extensive anterior acute myocardial infarction. | 2006-02 |
|
| Can nifekalant hydrochloride be used as a first-line drug for cardiopulmonary arrest (CPA)? : comparative study of out-of-hospital CPA with acidosis and in-hospital CPA without acidosis. | 2006-01 |
|
| Optical imaging of spiral waves: pharmacological modification of spiral-type excitations in a 2-dimensional layer of ventricular myocardium. | 2005-10 |
|
| Emergency treatment with nifekalant, a novel class III anti-arrhythmic agent, for life-threatening refractory ventricular tachyarrhythmias: post-marketing special investigation. | 2005-10 |
|
| Efficacy of nifekalant hydrochloride in the treatment of fatal ventricular arrhythmia in patients with ischemic heart disease. | 2005-07 |
|
| Enhancing electrical cardioversion and preventing immediate reinitiation of hemodynamically deleterious atrial fibrillation with class III drug pretreatment. | 2005-07 |
|
| Effect of nifekalant, a class III anti-arrhythmic agent, on Ca2+ waves in rat intact trabeculae. | 2005-06 |
|
| Effect of IKr blocker nifekalant on atrial action potential duration after successful internal cardioversion of chronic atrial fibrillation. | 2005-05 |
|
| Combined effects of nifekalant and lidocaine on the spiral-type re-entry in a perfused 2-dimensional layer of rabbit ventricular myocardium. | 2005-05 |
|
| Defibrillation effects of intravenous nifekalant in patients with out-of-hospital ventricular fibrillation. | 2005-01 |
|
| Sotalol-induced coronary spasm in a patient with dilated cardiomyopathy associated with sustained ventricular tachycardia. | 2004-11 |
|
| Development of a halothane-adrenaline arrhythmia model using in vivo Guinea pigs. | 2004-06 |
|
| Electropharmacological and proarrhythmic effects of a class III antiarrhythmic drug nifekalant hydrochloride assessed using the in vivo canine models. | 2004-05 |
|
| Effects of intravenous nifekalant, a class III antiarrhythmic drug, on atrial vulnerability parameters in patients with paroxysmal atrial fibrillation. | 2004-02 |
|
| IKr channel blockers: novel antiarrhythmic agents. | 2003-10 |
|
| [Effects of clinically available drugs on the repolarization process of the heart assessed by the in vivo canine models]. | 2003-06 |
|
| Inhibitory effect of the class III antiarrhythmic drug nifekalant on HERG channels: mode of action. | 2002-12-13 |
|
| Pretreatments with a novel pure potassium channel blocker, Nifekalant, were effective in the electrical atrial defibrillation: a report of two cases. | 2002-12 |
|
| [Recent findings on the dromotropic actions of the class III antiarrhythmic agents]. | 2002-11 |
|
| Anti-arrhythmic efficacy of nifekalant hydrochloride, a pure class III anti-arrhythmic agent, in patients with healed myocardial infarction and inducible sustained ventricular tachycardia. | 2002-11 |
|
| [Successful hybrid therapy combined with oral bepridil and ICD in a patient with amiodarone refractory life-threatening ventricular tachyarrhythmia associated with ischemic cardiomyopathy]. | 2002-09-01 |
|
| [Synthesis and vasorelaxant activities of benzopyran-4-one hydrazone derivatives]. | 2002-08 |
Sample Use Guides
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
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NCI_THESAURUS |
C47793
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NCI_THESAURUS |
C93038
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7478
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m7884
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100000084421
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NIFEKALANT
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CHEMBL360861
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C75132
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130636-43-0
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DTXSID7048374
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C076259
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SUB09254MIG
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5VZ7GZM43E
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1923
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4486
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
