BEPRIDIL HYDROCHLORIDE

US Previously Marketed

First approved in 1990

Details

Stereochemistry	RACEMIC
Molecular Formula	C24H34N2O.ClH.H2O
Molecular Weight	421.016
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.Cl.CC(C)COCC(CN(CC1=CC=CC=C1)C2=CC=CC=C2)N3CCCC3

InChI

InChIKey=UEECHQPWQHYEDE-UHFFFAOYSA-N

InChI=1S/C24H34N2O.ClH.H2O/c1-21(2)19-27-20-24(25-15-9-10-16-25)18-26(23-13-7-4-8-14-23)17-22-11-5-3-6-12-22;;/h3-8,11-14,21,24H,9-10,15-20H2,1-2H3;1H;1H2

HIDE SMILES / InChI

Description
Sources: http://www.rxlist.com/vascor-drug.htm
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/mtm/bepridil.html | http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1075 | https://www.ncbi.nlm.nih.gov/pubmed/1280569

Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It has inhibitory effects on both the slow calcium and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. It is used to treat hypertension (high blood pressure), angina (chest pain), sustained atrial fibrillation and tachyarrhythmia. The most common side effects were upper gastrointestinal complaints (nausea, dyspepsia or GI distress), diarrhea, dizziness, asthenia and nervousness. Certain drugs could increase the likelihood of potentially serious adverse effects with bepridil hydrochloride. In general, these are drugs that have one or more pharmacologic activities similar to bepridil hydrochloride, including anti-arrhythmic agents such as quinidine and procainamide, cardiac glycosides and tricyclic anti-depressants. Anti-arrhythmics and tricyclic anti-depressants could exaggerate the prolongation of the QT interval observed with bepridil hydrochloride. Cardiac glycosides could exaggerate the depression of AV nodal conduction observed with bepridil hydrochloride.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Beta-secretase (BACE) 5 Target ID: CHEMBL2111390 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20592218	Inhibitor 8504	6.0 µM [IC50]
Gamma-secretase 21 Target ID: CHEMBL2094135 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20592218	Modulator 846
potassium sodium-activated channel subfamily T member 1 3 Target ID: 57582.0 Gene Symbol: KCNT1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16876206	Inhibitor 8504	1.0 µM [IC50]
Voltage and receptor operated calcium channels 3 Target ID: Voltage and receptor operated calcium channels Sources: http://www.rxlist.com/vascor-drug.htm	Blocker 555

Conditions

Condition	Modality	Highest Phase	Product
Chronic stable angina 10 Sources: http://www.rxlist.com/vascor-drug.htm	Primary	Approved 8583	BEPRICOR Approved Use Bepridil hydrochloride is indicated for the treatment of chronic stable angina (classic effort-associated angina).
Hypertension 575 Sources: https://www.drugs.com/mtm/bepridil.html	Primary	Approved 8583	BEPRICOR Approved Use Bepridil is used to treat hypertension (high blood pressure) and to treat angina (chest pain).
Atrial fibrillation 131 Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1075	Primary	Approved 8583	BEPRICOR Approved Use It is usually used to treat sustained atrial fibrillation, tachyarrhythmia (ventricular) and angina.
Tachyarrhythmia 17 Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1075	Primary	Approved 8583	BEPRICOR Approved Use It is usually used to treat sustained atrial fibrillation, tachyarrhythmia (ventricular) and angina.

C_max

Value	Dose	Co-administered	Analyte	Population
806 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7650227	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		BEPRIDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
4.87 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7650227	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		BEPRIDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
38.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7650227	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		BEPRIDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.3% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3875635			BEPRIDIL plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 1 times / day steady, oral Studied dose Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 34-77 years Health Status: unhealthy Age Group: 34-77 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	Disc. AE: Weakness, Lightheadedness... AEs leading to discontinuation/dose reduction: Weakness (2 patients) Lightheadedness (1 patient) Syncopal attack (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 39-84 years Health Status: unhealthy Age Group: 39-84 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	Disc. AE: Electrocardiogram QTc interval prolonged... AEs leading to discontinuation/dose reduction: Electrocardiogram QTc interval prolonged (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
300 mg 1 times / day steady, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 43-80 years Health Status: unhealthy Age Group: 43-80 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	Disc. AE: Nausea, Diarrhea... AEs leading to discontinuation/dose reduction: Nausea (1 patient) Diarrhea (1 patient) Anorexia (1 patient) Bigeminy (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/	unhealthy, 63.5 years Health Status: unhealthy Age Group: 63.5 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/	Disc. AE: Ventricular tachycardia, Bradycardia... AEs leading to discontinuation/dose reduction: Ventricular tachycardia (1 patient) Bradycardia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/	unhealthy, 64.6 years Health Status: unhealthy Age Group: 64.6 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/	Disc. AE: Ventricular tachycardia, Bradycardia... AEs leading to discontinuation/dose reduction: Ventricular tachycardia (grade 5, 1 patient) Bradycardia (1 patient) Electrocardiogram QTc interval prolonged (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/

AEs

AE	Significance	Dose	Population
Lightheadedness	1 patient Disc. AE	400 mg 1 times / day steady, oral Studied dose Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 34-77 years Health Status: unhealthy Age Group: 34-77 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
Syncopal attack	1 patient Disc. AE	400 mg 1 times / day steady, oral Studied dose Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 34-77 years Health Status: unhealthy Age Group: 34-77 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
Weakness	2 patients Disc. AE	400 mg 1 times / day steady, oral Studied dose Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 34-77 years Health Status: unhealthy Age Group: 34-77 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
Electrocardiogram QTc interval prolonged	1 patient Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 39-84 years Health Status: unhealthy Age Group: 39-84 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
Anorexia	1 patient Disc. AE	300 mg 1 times / day steady, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 43-80 years Health Status: unhealthy Age Group: 43-80 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
Bigeminy	1 patient Disc. AE	300 mg 1 times / day steady, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 43-80 years Health Status: unhealthy Age Group: 43-80 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
Diarrhea	1 patient Disc. AE	300 mg 1 times / day steady, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 43-80 years Health Status: unhealthy Age Group: 43-80 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
Nausea	1 patient Disc. AE	300 mg 1 times / day steady, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: steady Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/	unhealthy, 43-80 years Health Status: unhealthy Age Group: 43-80 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3919556/
Bradycardia	1 patient Disc. AE	100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/	unhealthy, 63.5 years Health Status: unhealthy Age Group: 63.5 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/
Ventricular tachycardia	1 patient Disc. AE	100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/	unhealthy, 63.5 years Health Status: unhealthy Age Group: 63.5 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/
Bradycardia	1 patient Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/	unhealthy, 64.6 years Health Status: unhealthy Age Group: 64.6 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/
Electrocardiogram QTc interval prolonged	4 patients Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/	unhealthy, 64.6 years Health Status: unhealthy Age Group: 64.6 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/
Ventricular tachycardia	grade 5, 1 patient Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/	unhealthy, 64.6 years Health Status: unhealthy Age Group: 64.6 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19359813/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	inhibitor 2438	inhibitor 2507 substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2A6 879 CYP2E1 1060	CYP1A2 1197 P-gp 2052 BCRP 697

Drug as perpetrator

Target	Modality	Activity
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11344532/	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11344532/	no
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11344532/	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11344532/	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19702529/	yes
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/32906709/	yes

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28210973/	no
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19196847/	yes
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19196847/	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19196847/	yes
P-gp 2052	substrate 4014 Sources: https://www.futuremedicine.com/doi/abs/10.1517/14622416.2.4.401	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY565364	https://www.001chemical.com/chem/64706-54-3
3B Scientific (Wuhan) Corp	3B2-0571	http://www.3bsc.com/index/pro_info.php?id=19927
abcr GmbH	AB542520	http://www.abcr.com/shop/en/AB542520
Achemo Scientific Limited	AC-11145	http://www.achemo.com/search/?Keyword=64706-54-3
AHH Chemical co.,ltd	API-1541	http://www.ahhchemical.com/product/API-1541.html
AK Scientific, Inc. (AKSCI)	K042	http://www.aksci.com/item_detail.php?cat=K042
Angel Pharmatech	AG121309	http://www.angelpharmatech.com/64706-54-3.html
BLD Pharm	BD116381	http://www.bldpharm.com/products/64706-54-3.html
ChemMol	30105085	http://www.chemmol.com/chemmol/30105085.html
ChemMol	99124623	http://www.chemmol.com/chemmol/99124623.html
Chemspace	CSSB00000047941	https://chem-space.com/CSSB00000047941
CSNpharm	CSN10416	https://www.csnpharm.com/products/bepridil.html
Debye Scientific	DB-054717	http://www.debyesci.com/cas_64706-54-3.html
Finetech	FT-0630749	http://www.finetechnology-ind.com/prod/detail/pub/64706-54-3.html
Glentham Life Sciences	GP4395	http://www.glentham.com/products/product/GP4395/
Lab Network	LN00330174	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00330174
Molcore	MC565364	https://www.molcore.com/product/64706-54-3
Smolecule	S520991	http://www.smolecule.com/products/s520991
Smolecule	S772535	https://www.smolecule.com/products/s772535
THE BioTek	bt-261730	https://www.thebiotek.com/product/inhibitors/bt-261730
THE BioTek	bt-311849	https://www.thebiotek.com/product/others/bt-311849
Vesino Industrial Co Ltd	VA10387	http://www.vsnchem.com/goto/product/23859/

PubMed

Title	Date	PubMed
Evaluation of bepridil efficacy by electrophysiologic testing in patients with recurrent ventricular tachycardia: comparison of two regimens.	1992 Apr	1390333
Biliary drug lithiasis: dipyridamole gallstones.	1992 Nov 28	1360065
Antioxidant benzoylated flavan-3-ol glycoside from Celastrus orbiculatus.	2001 Jan	11170672
Electron spin resonance assessment of the antioxidant potential of medicinal plants. Part I. Contribution of anthocyanosides and flavonoids to the radical scavenging ability of fruit and herbal teas.	2001 Jul-Aug	11693734
DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity of flavonoids obtained from some medicinal plants.	2001 Oct	11642334
Scavenging of free radicals, antimicrobial, and cytotoxic activities of the Maillard reaction products of beta-lactoglobulin glycated with several sugars.	2001 Oct	11600062
Antioxidant activities of dioscorin, the storage protein of yam (Dioscorea batatas Decne) tuber.	2001 Oct	11600050
Identification and antioxidant activity of novel chlorogenic acid derivatives from bamboo (Phyllostachys edulis).	2001 Oct	11600002
Vasorelaxing and antioxidant constituents from Hernandia nymphaeifolia.	2001 Oct	11582533
Interaction of bepridil with the cardiac troponin C/troponin I complex.	2001 Sep 28	11591369
Antagonistic effects of 24R,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 on L-type Ca2+ channels and Na+/Ca2+ exchange in enterocytes from Atlantic cod (Gadus morhua).	2002 Feb	11854099
Role of Na(+)-Ca(2+) exchanger after traumatic or hypoxic/ischemic injury to spinal cord white matter.	2002 Jan-Feb	14588286
Free radical scavenging activity of red ginseng aqueous extracts.	2002 Mar 20	11882354
Usefulness and safety of bepridil in converting persistent atrial fibrillation to sinus rhythm.	2003 Aug 15	12914884
A case of bepridil induced interstitial pneumonitis.	2003 Dec	14617550
Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP.	2003 Dec 17	14684870
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.	2003 Nov 17	14612892
A case of sick sinus syndrome that developed torsades de pointes, pacing failure and sensing failure during administration of bepridil.	2003 Sep	14587660
Bepridil block of recombinant human cardiac IKs current shows a time-dependent unblock.	2004 Feb	14716203
Differential effect of HERG blocking agents on cardiac electrical alternans in the guinea pig.	2004 Feb 20	14975710
Atrial fibrillatory frequency, atrial fibrillatory rate, or atrial cycle length--does it matter?	2004 Jul 1	15219531
Evidence for a protective role played by the Na+/Ca2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats.	2004 Mar	14975699

Patents

Sample Use Guides

In Vivo Use Guide

Initial dose: 200 mg once a day. Maintenance dose: 300-400 mg once a day.

Route of Administration: Oral

In Vitro Use Guide

In APP-overexpressing HEK293 cells lower Ab38, Ab40 and Ab42 generation was detected after Bepridil treatment (30 uM) for 16 h.

Name

Type

Language

BEPRIDIL HYDROCHLORIDE MONOHYDRATE

Preferred Name

English

BEPRIDIL HYDROCHLORIDE

Official Name

English

Bepridil hydrochloride monohydrate [WHO-DD]

Common Name

English

1-PYRROLIDENEETHANAMINE, .BETA.-((2-METHYLPROPOXY)METHYL)-N-PHENYL-N-(PHENYLMETHYL)-, MONOHYDROCHLORIDE, MONOHYDRATE

Common Name

English

BEPRIDIL HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

CERM 1978

Code

English

BEPADIN

Brand Name

English

NSC-758390

Code

English

UNICORDIUM

Brand Name

English

1-[2-(N-Benzylanilino)-1-(isobutoxymethyl)ethyl]-pyrrolidine monohydrochloride monohydrate

Systematic Name

English

BEPRIDIL HYDROCHLORIDE [MART.]

Common Name

English

BEPRIDIL HYDROCHLORIDE [VANDF]

Common Name

English

CORDIUM

Brand Name

English

BEPRIDIL HYDROCHLORIDE HYDRATE

Common Name

English

BEPRIDIL HYDROCHLORIDE HYDRATE [JAN]

Common Name

English

BEPRIDIL HYDROCHLORIDE MONOHYDRATE [MI]

Common Name

English

CERM-1978

Code

English

VASCOR

Brand Name

English

BEPRIDIL HYDROCHLORIDE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C333