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

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

Description

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 76	Blocker 537
Calmodulin 17	Inhibitor 8,297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Atrial fibrillation 131	Preventing		Not Provided 504	Unknown
Ventricular arrhythmia 50	Primary		Approved 8,429	FIBORAN

C_max

Value	Dose	Analyte	Population
0.055 μg/mL	25 mg single, oral	APRINDINE plasma	Homo sapiens
0.12 μg/mL	50 mg single, oral	APRINDINE plasma	Homo sapiens
0.59 μg/mL	100 mg single, oral	APRINDINE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
0.43 μg × h/mL	25 mg single, oral	APRINDINE plasma	Homo sapiens
1.16 μg × h/mL	50 mg single, oral	APRINDINE plasma	Homo sapiens
9.16 μg × h/mL	100 mg single, oral	APRINDINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
8 h	25 mg single, oral	APRINDINE plasma	Homo sapiens
9.4 h	50 mg single, oral	APRINDINE plasma	Homo sapiens
15.8 h	100 mg single, oral	APRINDINE plasma	Homo sapiens

F_unbound

Value	Dose	Analyte	Population
95.5%	25 mg single, oral	APRINDINE plasma	Homo sapiens
95.5%	50 mg single, oral	APRINDINE plasma	Homo sapiens
95.5%	100 mg single, oral	APRINDINE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
400 mg single, intravenous Higher than recommended	unhealthy, ADULT	Disc. AE: Ventricular tachycardia...
200 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT	Disc. AE: Ventricular tachycardia...
40 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT	Disc. AE: Exanthema, AST increased...

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AEs

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AE	Significance	Dose	Population
Ventricular tachycardia	Disc. AE	400 mg single, intravenous Higher than recommended	unhealthy, ADULT
Ventricular tachycardia	Disc. AE	200 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT
ALT increased	2.1% Disc. AE	40 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT
AST increased	2.1% Disc. AE	40 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT
Exanthema	2.1% Disc. AE	40 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737		inhibitor 1,852 substrate 1,217	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1,461 CYP1A2 1,524

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 1,692	inhibitor 3,277	weak [IC50 154 uM]
P-gp 1,650	inhibitor 3,277	weak [Inhibition 100 uM]
CYP2D6 1,891	inhibitor 3,277	yes [Ki 0.017 uM]

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1,217	substrate 3,367	yes [Km 0.35 uM]
CYP3A4 1,737	substrate 3,367	yes		yes (co-administration study)

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

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PubMed

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Title	Date	PubMed
[Accident during local anesthesia in a patient with antiarrhythmic therapy].	1975 Jul	51544
New drugs for treating cardiac arrhythmias.	1981 Jan	6780988
Effective plasma concentrations of aprindine in canine ventricular arrhythmias.	1984 Jan-Feb	6199593
Effect of sotalol, aprindine and their combination on maximum upstroke velocity of action potential in guinea-pig papillary muscle.	1986 Nov 19	3816955
Broad sensitivity of rodent arrhythmia models to class I, II, III, and IV antiarrhythmic agents.	1989 Jun	2726785

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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.

Show entries

Name

Type

Language

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

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Classification Tree

Code System

Code

Agent Affecting Cardiovascular System

NCI_THESAURUS

C47793

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Code System

Code

Type

Description

DRUG BANK

DBSALT000917

PRIMARY

MERCK INDEX

m2013

PRIMARY

Merck Index

CAS

33237-74-0

PRIMARY

EPA CompTox

DTXSID5046726

PRIMARY

EVMPD

SUB00565MIG

PRIMARY

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ACTIVE MOIETY


					5Y48085P9Q

APRINDINE

SUBSTANCE RECORD


					PB5EKT7Q2V

APRINDINE HYDROCHLORIDE

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator