APRINDINE HYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H30N2.ClH
Molecular Weight	358.948
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CCN(CC)CCCN(C1CC2=C(C1)C=CC=C2)C3=CC=CC=C3

InChI

InChIKey=KIPFVRHNAAZJOD-UHFFFAOYSA-N

InChI=1S/C22H30N2.ClH/c1-3-23(4-2)15-10-16-24(21-13-6-5-7-14-21)22-17-19-11-8-9-12-20(19)18-22;/h5-9,11-14,22H,3-4,10,15-18H2,1-2H3;1H

HIDE SMILES / InChI

Molecular Formula	C22H30N2
Molecular Weight	322.487
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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

Description
Sources: http://www.ndrugs.com/?s=aprindine
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/6186851

Aprindine is a class Ib antiarrhythmic agent. It is not approved in USA, but is available in European countries, where it is used to treat supraventricular and ventricular arrhythmias. Aprindine acts by blocking sodium voltage channels and disrupting interactions between calmodulin and prosphodiesterase.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium channel alpha subunit 72 Target ID: CHEMBL2331043 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1660104	Blocker 555
Calmodulin 17 Target ID: CHEMBL6093 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6186851	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Atrial fibrillation 131 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12074271	Preventing		Not Provided 511	Unknown Approved Use Unknown
Ventricular arrhythmia 50 Sources: http://flexikon.doccheck.com/de/Aprindin	Primary		Approved 8583	FIBORAN Approved Use Aprindine is indicated for treatment of therapy-resistant ventricular tachycardias and ventricular extrasystoles.

C_max

Value	Dose	Analyte	Population
0.055 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.12 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.59 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
0.43 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.16 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9.16 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Analyte	Population
95.5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
95.5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
95.5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6714286/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	APRINDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
400 mg single, intravenous Higher than recommended Dose: 400 mg Route: intravenous Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7039289/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7039289/	Disc. AE: Ventricular tachycardia... AEs leading to discontinuation/dose reduction: Ventricular tachycardia Sources: https://pubmed.ncbi.nlm.nih.gov/7039289/
200 mg 1 times / day multiple, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7039289/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7039289/	Disc. AE: Ventricular tachycardia... AEs leading to discontinuation/dose reduction: Ventricular tachycardia Sources: https://pubmed.ncbi.nlm.nih.gov/7039289/
40 mg 1 times / day multiple, oral Studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12074271/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12074271/	Disc. AE: Exanthema, AST increased... AEs leading to discontinuation/dose reduction: Exanthema (2.1%) AST increased (2.1%) ALT increased (2.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/12074271/

AEs

AE	Significance	Dose	Population
Ventricular tachycardia	Disc. AE	400 mg single, intravenous Higher than recommended Dose: 400 mg Route: intravenous Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7039289/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7039289/
Ventricular tachycardia	Disc. AE	200 mg 1 times / day multiple, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7039289/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7039289/
ALT increased	2.1% Disc. AE	40 mg 1 times / day multiple, oral Studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12074271/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12074271/
AST increased	2.1% Disc. AE	40 mg 1 times / day multiple, oral Studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12074271/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12074271/
Exanthema	2.1% Disc. AE	40 mg 1 times / day multiple, oral Studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12074271/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12074271/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946		inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 CYP1A2 2153

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/9578183/	weak [IC50 154 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyMTMwMzMifX0=	weak [Inhibition 100 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/8485023/	yes [Ki 0.017 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8485023/	yes [Km 0.35 uM]
CYP3A4 1946	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/jscpt1970/30/3/30_3_571/_article/-char/en	yes		yes (co-administration study) Comment: Verapamil increased aprindine AUC by 2.35-fold. Sources: https://www.jstage.jst.go.jp/article/jscpt1970/30/3/30_3_571/_article/-char/en

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/10517660/

PubMed

Title	Date	PubMed
Inflammatory cytokines and atrial fibrillation: current and prospective views.	2010	22096359
Enantioselective plasma protein binding of propafenone: mechanism, drug interaction, and species difference.	2009-07	18937289
Effects of antiarrhythmic drugs on the hyperpolarization-activated cyclic nucleotide-gated channel current.	2009-06	19498275
Relationship between serum aprindine concentration and neurologic side effects in Japanese.	2009-04	19336897
Na+/Ca2+ exchange inhibitors: a new class of calcium regulators.	2007-09	17896959
Relation of interleukin-6 and C-reactive protein levels to sinus maintenance after pharmacological cardioversion in persistent atrial fibrillation.	2007-09	17878753
Pharmacological cardioversion of long-lasting atrial fibrillation.	2007	17587743
Topics on the Na+/Ca2+ exchanger: pharmacological characterization of Na+/Ca2+ exchanger inhibitors.	2006-09	16990699
Pharmacological cardioversion of persistent atrial fibrillation with and without a history of drug-resistant paroxysmal atrial fibrillation.	2006-09	16936425
[Strategy for cardiac arrhythmias in acute coronary syndrome].	2006-04	16613191
Nonlinear mixed effects model analysis of the pharmacokinetics of routinely administered bepridil in Japanese patients with arrhythmias.	2006-03	16508157
Effect of antiarrhythmic agents on heart rate variability indices after myocardial infarction: comparative experimental study of aprindine and procainamide.	2005-10	16275488
Proteasomal degradation of Kir6.2 channel protein and its inhibition by a Na+ channel blocker aprindine.	2005-06-17	15882977
Appropriate dosing of antiarrhythmic drugs in Japan requires therapeutic drug monitoring.	2005-02	15658999
Drug-induced changes in fibrillation cycle length and organization index can predict chemical cardioversion of long-lasting atrial fibrillation with bepridil alone or in combination with aprindine.	2004-12	15564697
Maintenance of sinus rhythm and recovery of atrial mechanical function after cardioversion with bepridil or in combination with aprindine in long-lasting persistent atrial fibrillation.	2004-09	15329504
Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome.	2004-02	15028050
Theoretical possibilities for the development of novel antiarrhythmic drugs.	2004-01	14754422
Role of atrial fibrillation threshold evaluation on guiding treatment.	2003-10-01	16943922
Usefulness and safety of bepridil in converting persistent atrial fibrillation to sinus rhythm.	2003-08-15	12914884
[Comparison of the efficacies of disopyramide, cibenzoline and aprindine for the termination of paroxysmal and persistent atrial fibrillation in elderly and non-elderly patients].	2003-04	12728540
Atrial fibrillation threshold predicted long-term efficacy of pharmacological treatment of patients without structural heart disease.	2002-10	12408258
Double-blind placebo-controlled trial of aprindine and digoxin for the prevention of symptomatic atrial fibrillation.	2002-06	12074271
Inhibitory effect of aprindine on Na+/Ca2+ exchange current in guinea-pig cardiac ventricular myocytes.	2002-06	12023938
Nonlinear pharmacokinetics of aprindine in guinea pigs.	2002	15618680
Inhibitory effects of aprindine on the delayed rectifier K+ current and the muscarinic acetylcholine receptor-operated K+ current in guinea-pig atrial cells.	1999-02	10188988
Prediction of catalepsies induced by amiodarone, aprindine and procaine: similarity in conformation of diethylaminoethyl side chain.	1998-11	9808703
Effects of aprindine on ischemia/reperfusion-induced cardiac contractile dysfunction of perfused rat heart.	1996-03	8935716
Complex frequency-dependent interaction of class-I antiarrhythmic drugs as they affect intraventricular conduction.	1995-06	7588928
Hepatocellular peroxisomes in human alcoholic and drug-induced hepatitis: a quantitative study.	1991-11	1937386
Combined application of class I antiarrhythmic drugs causes "additive", "reductive", or "synergistic" sodium channel block in cardiac muscles.	1990-11	2176934
Cardioprotective effects of various class I antiarrhythmic drugs in canine hearts.	1989-07	2738264
Broad sensitivity of rodent arrhythmia models to class I, II, III, and IV antiarrhythmic agents.	1989-06	2726785
Effect of sotalol, aprindine and their combination on maximum upstroke velocity of action potential in guinea-pig papillary muscle.	1986-11-19	3816955
Effective plasma concentrations of aprindine in canine ventricular arrhythmias.	1984-01-01	6199593
Quantitative analysis of the antiarrhythmic effect of drugs on canine ventricular arrhythmias by the determination of minimum effective plasma concentrations.	1983-01	6827775
New drugs for treating cardiac arrhythmias.	1981-01	6780988
Antiarrhythmic and antifibrillatory properties of aprindine.	1975-08	1151768
[Accident during local anesthesia in a patient with antiarrhythmic therapy].	1975-07	51544

Patents

Sample Use Guides

In Vivo Use Guide

150-200 mg daily in divided doses, up to 300 mg/day may be used under strict observation for the first 2-3 days if needed.

Route of Administration: Oral

In Vitro Use Guide

Effects of aprindine (3 umol/l) on the Na+ current using whole cell voltage clamp was studied in guinea-pig ventricular myocytesd. Aprindine revealed tonic block (Kdrest = 37.7 umol/l, Kdi = 0.74 umol/l) and shifted inactivation curve to hyperpolarizing direction by 11.4+3.5 mV (n = 4) without changes in slope factor.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:59:40 GMT 2025` Edited by `admin` on `Mon Mar 31 17:59:40 GMT 2025`
Record UNII	PB5EKT7Q2V
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ASPENON

Preferred Name

English

APRINDINE HYDROCHLORIDE

Official Name

English

APRINDINE HYDROCHLORIDE [MI]

Common Name

English

APRINDINE HYDROCHLORIDE [JAN]

Common Name

English

COMPOUND 83846

Code

English

COMPOUND-83846

Code

English

NSC-284614

Code

English

APRINDINE HCL

Common Name

English

APRINIDINE CHLORIDE

Common Name

English

APRINDINE HYDROCHLORIDE [MART.]

Common Name

English

APRINDINE HYDROCHLORIDE [USAN]

Common Name

English

Aprindine hydrochloride [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47793