ZATEBRADINE HYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H36N2O5.ClH
Molecular Weight	493.035
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.COC1=CC=C(CCN(C)CCCN2CCC3=C(CC2=O)C=C(OC)C(OC)=C3)C=C1OC

InChI

InChIKey=ZRNKXJHEQKMWCH-UHFFFAOYSA-N

InChI=1S/C26H36N2O5.ClH/c1-27(13-9-19-7-8-22(30-2)23(15-19)31-3)11-6-12-28-14-10-20-16-24(32-4)25(33-5)17-21(20)18-26(28)29;/h7-8,15-17H,6,9-14,18H2,1-5H3;1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20795648
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15648302 | https://www.ncbi.nlm.nih.gov/pubmed/14561092 | https://www.ncbi.nlm.nih.gov/pubmed/19093365

Zatebradine is a bradycardic compound that blocks hyperpolarization-activated inward current (If) through cyclic nucleotide-gated cation (HCN) channels in sinoatrial node cells. Additionally, it can block voltage-gated outward K+ (IK) currents and related neuronal hyperpolarization-activated inward current (Ih) channels but exhibits little or no activity for L-type Ca2+ (ICa) currents. When assessed through telemetric ECG recording in mice, zatebradine reduced heart rate from 600 to 200 beats per minute with an ED50 value of 1.8 mg/kg and induced increasing arrhythmia at concentrations >10 mg/kg.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 14 Target ID: CHEMBL1250417 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20795648	Blocker 537		8.57 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Myocardial infarction 121 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19093365	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Bradycardic and proarrhythmic properties of sinus node inhibitors.	2006 Apr	16387796

Patents

Sample Use Guides

In Vivo Use Guide

Rats were treated with Zatebradine at dose 3 mg/kg i.v

Route of Administration: Intravenous

In Vitro Use Guide

Sinoatrial node pacemaker cells were isolated enzymatically from rabbit hearts. The inward currents, elicited by hyperpolarizing pulses of 2000 ms from a holding potential of −40 mV to −140 mV in 10 mV increments and then clamp back to 0 mV for 1000 ms, were recorded first in the absence and then in the presence of zatebradine or CsCl. The established If blockers zatebradine (1 mkM) and CsCl (2 mM) inhibited If by 63.7 ± 8.4% and 91.8 ± 5.6%, respectively

Name

Type

Language

ZATEBRADINE HYDROCHLORIDE

Common Name

English

3-(3-((2-(3,4-DIMETHOXYPHENYL)ETHYL)METHYLAMINO)PROPYL)-1,3,4,5-TETRAHYDRO-7,8-DIMETHOXY-2H-3-BENZAZEPIN-2-ONE, HYDROCHLORIDE

Systematic Name

English

2H-3-BENZAZEPIN-2-ONE, 3-(3-((2-(3,4-DIMETHOXYPHENYL)ETHYL)METHYLAMINO)PROPYL)-1,3,4,5-TETRAHYDRO-7,8-DIMETHOXY-, HYDROCHLORIDE (1:1)

Systematic Name

English

UL-FS-49

Code

English

ZATEBRADINE HYDROCHLORIDE [MI]

Common Name

English

ULFS-49CL

Code

English

Code System Code Type Description

PUBCHEM

3045335