Page last updated: 2024-12-06

zatebradine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Cross-References

ID SourceID
PubMed CID65637
CHEMBL ID69679
CHEBI ID93613
SCHEMBL ID295751
MeSH IDM0128281

Synonyms (41)

Synonym
gtpl2358
ul-fs49
zatebradina [inn-spanish]
3-(3-((3,4-dimethoxyphenethyl)methylamino)propyl)-1,3,4,5-tetrahydro-7,8-dimethoxy-2h-3-benzazepin-2-one
zatebradine ,
zatebradine [inn]
zatebradinum [inn-latin]
CHEMBL69679 ,
3-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1h-3-benzazepin-4-one
85175-67-3
bdbm50326988
3-(3-{[2-(3,4-dimethoxy-phenyl)-ethyl]-methyl-amino}-propyl)-7,8-dimethoxy-1,3,4,5-tetrahydro-benzo[d]azepin-2-one
unii-tv27ry5876
tv27ry5876 ,
zatebradinum
zatebradina
zatebradine [mi]
BRD-K92446736-003-01-4
SCHEMBL295751
1-[7,8-dimethoxy-1,3,4,5-tetrahydro-2h-3-benzazepin-2-on-3-yl]-3-[n-methyl-n-(2-{3,4-dimethoxy-phenyl}-ethyl)-amino]-propane
KEDQCFRVSHYKLR-UHFFFAOYSA-N
1-[7,8-dimethoxy-1,3,4,5-tetrahydro-2h-3-benzazepin-2-on-3-yl]-3-[n-methyl-n-(2-{3,4-dimethoxy-phenyl}ethyl)-amino]-propane
CS-3620
DTXSID1048413
zatabradine
mfcd00867014
HY-13422A
AKOS030213235
CHEBI:93613
BCP16190
FT-0729624
3-(3-((3,4-dimethoxyphenethyl)(methyl)amino)propyl)-7,8-dimethoxy-4,5-dihydro-1h-benzo[d]azepin-2(3h)-one
Q27089283
125846-52-8
ul-fs-49 (free base);ul-fs-49cl (free base)
benzenesulfonamide,5-amino-2-methyl-
ul-fs-49cl free base
ul-fs-49 free base
A914810
F85097
MS-28329

Research Excerpts

Overview

Zatebradine is a drug with a specific bradycardiac electrophysiological profile. It inhibits the hyperpolarization-activated current (I(f) in the rabbit sinoatrial node.

ExcerptReferenceRelevance
"Zatebradine (UL-FS 49) is a drug with a specific bradycardiac electrophysiological profile. "( Use-dependent block of the pacemaker current I(f) in rabbit sinoatrial node cells by zatebradine (UL-FS 49). On the mode of action of sinus node inhibitors.
Goethals, M; Raes, A; van Bogaert, PP, 1993
)
1.95
"Zatebradine is a bradycardic agent that inhibits the hyperpolarization-activated current (I(f)) in the rabbit sinoatrial node. "( Class III antiarrhythmic effects of zatebradine. Time-, state-, use-, and voltage-dependent block of hKv1.5 channels.
Delpón, E; Franqueza, L; Gay, P; Pérez, O; Snyders, DJ; Tamargo, J; Valenzuela, C, 1996
)
2.01
"Zatebradine is a new specific bradycardiac agent that selectively slows the depolarization in the pacemaker cells of the sinoatrial node. "( Role of zatebradine and propranolol in attenuation of tachycardia produced by dobutamine in pigs.
Dimich, I; Mezrow, C; Neustein, SM; Shiang, H, 1997
)
2.17
"Zatebradine is a bradycardic agent with a selective effect on the pacemaker current in the sinus node. "( The effect of sinus node depression on heart rate variability in humans using zatebradine, a selective bradycardic agent.
Dorian, P; Green, M; Khaykin, Y; Mitchell, J; Newman, D; Tang, A; Wulffhart, Z,
)
1.8

Treatment

Treatment with zatebradine enhances both BRS and HRV. The incidence of ventricular and supraventricular premature beats during defeat increased 2.5-fold and 3.5 -fold, respectively.

ExcerptReferenceRelevance
"In zatebradine/vehicle-treated rats, the incidence of ventricular and supraventricular premature beats during defeat increased 2.5-fold and 3.5-fold, respectively."( 8-OH-DPAT prevents cardiac arrhythmias and attenuates tachycardia during social stress in rats.
Mastorci, F; Nalivaiko, E; Sgoifo, A, 2009
)
0.87
"Treatment with zatebradine enhances both BRS and HRV."( The bradycardic agent zatebradine enhances baroreflex sensitivity and heart rate variability in rats early after myocardial infarction.
Ehmke, H; Haass, M; Krüger, C; Kübler, W; Landerer, V; Zugck, C, 2000
)
0.96

Pharmacokinetics

ExcerptReferenceRelevance
" After oral administration, a mean peak concentration in plasma of 24."( Zatebradine: pharmacokinetics of a novel heart-rate-lowering agent after intravenous infusion and oral administration to healthy subjects.
Bauer, E; Cornelissen, PJ; Heinzel, G; Jonkman, JH; Roth, W; van Tol, RG; Zuiderwijk, PB, 1993
)
1.73

Dosage Studied

ExcerptRelevanceReference
" In isolated guinea-pig atria UL-FS 49 antagonized the carbachol-induced bradycardia; a 10-fold shift of the dose-response curve (CA10) was achieved with 11."( Cardiovascular characterization of UL-FS 49, 1,3,4,5-tetrahydro-7,8-dimethoxy-3-[3-][2-(3,4-dimethoxyphenyl)ethyl] methylimino]propyl]-2H-3-benzazepin-2-on hydrochloride, a new "specific bradycardic agent".
Kobinger, W; Lillie, C, 1984
)
0.27
" Drugs were dosed cumulatively after the second, fourth and sixth exercise periods."( The haemodynamic actions of ZENECA ZD7288, a novel sino-atrial node function modulator, in the exercising beagle: a comparison with zatebradine and propranolol.
Johnson, IR; Rouse, W; Stafford, PJ, 1994
)
0.49
" Hypothermia shifted the dose-response curves to the right for the negative chronotropic and inotropic effects of verapamil and for the negative chronotropic and positive inotropic effects of zatebradine, but not for the negative chronotropic and positive inotropic effects of E-4031."( Effects of low temperature on the chronotropic and inotropic responses to zatebradine, E-4031 and verapamil in isolated perfused dog atria.
Chiba, S; Furukawa, Y; Hoyano, Y; Kasama, M; Oguchi, T, 1998
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
benzazepineA group of two-ring heterocyclic compounds consisting of a benzene ring fused to an azepine ring.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (3)

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2Mus musculus (house mouse)EC50 (µMol)5.45004.52004.98505.4500AID515584
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1Mus musculus (house mouse)EC50 (µMol)16.78004.50004.50004.5000AID515582
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)EC50 (µMol)8.57004.28006.42508.5700AID515585
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (19)

Processvia Protein(s)Taxonomy
regulation of heart ratePotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
sinoatrial node developmentPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
regulation of membrane depolarizationPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
monoatomic cation transportPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
muscle contractionPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
blood circulationPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
sodium ion transmembrane transportPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
regulation of membrane potentialPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
regulation of cardiac muscle contractionPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
cellular response to cAMPPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
cellular response to cGMPPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
potassium ion transmembrane transportPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
membrane depolarization during cardiac muscle cell action potentialPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
SA node cell action potentialPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
membrane depolarization during SA node cell action potentialPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
sodium ion import across plasma membranePotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
regulation of cardiac muscle cell action potential involved in regulation of contractionPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
potassium ion import across plasma membranePotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (7)

Processvia Protein(s)Taxonomy
intracellularly cAMP-activated cation channel activityPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
voltage-gated sodium channel activityPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
voltage-gated potassium channel activityPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
protein bindingPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
cAMP bindingPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
identical protein bindingPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
voltage-gated potassium channel activity involved in SA node cell action potential depolarizationPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (5)

Processvia Protein(s)Taxonomy
plasma membranePotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
perinuclear region of cytoplasmPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
HCN channel complexPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
axonPotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
dendritePotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (17)

Assay IDTitleYearJournalArticle
AID174736Bradycardic activity was evaluated in an anesthetized rat model as percent heart rate(beats/min) reduction 20 min after iv injection of 5 mg/kg1991Journal of medicinal chemistry, Mar, Volume: 34, Issue:3
Specific bradycardic agents. 2. Heteroaromatic modifications in the side chain of specific bradycardic benzazepinones: chemistry, pharmacology, and structure-activity relationships.
AID170902Percentage change in heart rate from the initial value in urethane-anesthetized rats at 3 mg/kg intravenous dose2003Bioorganic & medicinal chemistry letters, Jul-07, Volume: 13, Issue:13
(+/-)-2-(3-Piperidyl)-1,2,3,4-tetrahydroisoquinolines as a new class of specific bradycardic agents.
AID80305Concentration required to produce 30% reduction from the initial beat rates in isolated guinea pig right atria.2004Bioorganic & medicinal chemistry letters, Jun-21, Volume: 14, Issue:12
Synthesis and pharmacological evaluation of piperidinoalkanoyl-1,2,3,4-tetrahydroisoquinoline derivatives as novel specific bradycardic agents.
AID515582Blockade of mouse HCN1 expressed in HEK293 cells at -120 f-current amplitude by patch-clamp electrophysiological assay2010Journal of medicinal chemistry, Sep-23, Volume: 53, Issue:18
Design, synthesis, and preliminary biological evaluation of new isoform-selective f-current blockers.
AID78479Concentration required to produce 30% reduction (in vitro) from the initial spontaneous beat rates in isolated guinea pig atrium2003Bioorganic & medicinal chemistry letters, Jul-07, Volume: 13, Issue:13
(+/-)-2-(3-Piperidyl)-1,2,3,4-tetrahydroisoquinolines as a new class of specific bradycardic agents.
AID174738Bradycardic activity was evaluated in an anesthetized rat model as percent heart rate(beats/min) reduction 5 min after iv injection of 5 mg/kg1991Journal of medicinal chemistry, Mar, Volume: 34, Issue:3
Specific bradycardic agents. 2. Heteroaromatic modifications in the side chain of specific bradycardic benzazepinones: chemistry, pharmacology, and structure-activity relationships.
AID515585Blockade of human HCN4 expressed in HEK293 cells at -120 f-current amplitude by patch-clamp electrophysiological assay2010Journal of medicinal chemistry, Sep-23, Volume: 53, Issue:18
Design, synthesis, and preliminary biological evaluation of new isoform-selective f-current blockers.
AID515586Blockade of HCN in guinea pig spontaneously beating atria assessed as reduction of heart rate measured for 15 mins2010Journal of medicinal chemistry, Sep-23, Volume: 53, Issue:18
Design, synthesis, and preliminary biological evaluation of new isoform-selective f-current blockers.
AID233631Ratio of heart rate reduction to mean arterial blood pressure reduction1991Journal of medicinal chemistry, Mar, Volume: 34, Issue:3
Specific bradycardic agents. 2. Heteroaromatic modifications in the side chain of specific bradycardic benzazepinones: chemistry, pharmacology, and structure-activity relationships.
AID234467Delta HR ratio measured as the ratio of delta HR(20 min)/delta HR (5 min)1991Journal of medicinal chemistry, Mar, Volume: 34, Issue:3
Specific bradycardic agents. 2. Heteroaromatic modifications in the side chain of specific bradycardic benzazepinones: chemistry, pharmacology, and structure-activity relationships.
AID1633631Inhibition of human HCN4 expressed in HEK293 cells assessed as reduction in hyperpolarization activated current at 10 uM at holding potential of -80 mV by patch clamp assay relative to control2019ACS medicinal chemistry letters, Apr-11, Volume: 10, Issue:4
EC18 as a Tool To Understand the Role of HCN4 Channels in Mediating Hyperpolarization-Activated Current in Tissues.
AID174740Hypotensive activity was evaluated in an anesthetized rat model as percent mean aortic blood pressure(mm hg) reduction 5 min after iv injection of 5 mg/kg1991Journal of medicinal chemistry, Mar, Volume: 34, Issue:3
Specific bradycardic agents. 2. Heteroaromatic modifications in the side chain of specific bradycardic benzazepinones: chemistry, pharmacology, and structure-activity relationships.
AID515584Blockade of mouse HCN2 expressed in HEK293 cells at -120 f-current amplitude by patch-clamp electrophysiological assay2010Journal of medicinal chemistry, Sep-23, Volume: 53, Issue:18
Design, synthesis, and preliminary biological evaluation of new isoform-selective f-current blockers.
AID1346525Human HCN1 (Cyclic nucleotide-regulated channels)2006Molecular pharmacology, Apr, Volume: 69, Issue:4
Bradycardic and proarrhythmic properties of sinus node inhibitors.
AID1346522Human HCN3 (Cyclic nucleotide-regulated channels)2006Molecular pharmacology, Apr, Volume: 69, Issue:4
Bradycardic and proarrhythmic properties of sinus node inhibitors.
AID1346524Human HCN2 (Cyclic nucleotide-regulated channels)2006Molecular pharmacology, Apr, Volume: 69, Issue:4
Bradycardic and proarrhythmic properties of sinus node inhibitors.
AID1346517Human HCN4 (Cyclic nucleotide-regulated channels)2006Molecular pharmacology, Apr, Volume: 69, Issue:4
Bradycardic and proarrhythmic properties of sinus node inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (124)

TimeframeStudies, This Drug (%)All Drugs %
pre-199013 (10.48)18.7374
1990's71 (57.26)18.2507
2000's26 (20.97)29.6817
2010's13 (10.48)24.3611
2020's1 (0.81)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 20.59

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index20.59 (24.57)
Research Supply Index4.93 (2.92)
Research Growth Index4.94 (4.65)
Search Engine Demand Index21.17 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (20.59)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials6 (4.55%)5.53%
Reviews5 (3.79%)6.00%
Case Studies1 (0.76%)4.05%
Observational0 (0.00%)0.25%
Other120 (90.91%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]