DK-AH 269

Names

[ Name ]:
DK-AH 269

[Synonym ]:
DK-AH 269
(S)-(+)-7,8-Dimethoxy-3-[[1-(2-(3,4-dimethoxyphenyl)ethyl)-3-piperidinyl]methyl]-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one hydrochloride
3-[[(3S)-1-[2-(3,4-dimethoxyphenyl)ethyl]piperidin-3-yl]methyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one,hydrochloride
DK-AH 269
Cilobradine (hydrochloride)

Biological Activity

[Description]:

Cilobradine is an HCN Channel blocker; an open channel blocker of neuronal Ih and related cardiac If channels.Target: HCN Channel blockerCilobradine is a HCN channel blocker that is about 3 times more potent than ZD7288. At a concentration of 10 μM, Cilobradine inhibits WT mHCN2 channel current by 86 ± 2% (n = 5). In contrast, I432A and A425G channel currents were only reduced by 14 ± 1% (n = 4) and 19 ± 2% (n = 8), respectively, by this concentration of Cilobradine. The double mutant (I432A/A425G) channel was even less sensitive to 10 μM Cilobradine (8 ± 2% inhibition; n = 4).

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> HCN Channel

Research Areas >> Cardiovascular Disease

[References]

[1]. Cheng L, et al. Molecular mapping of the binding site for a blocker of hyperpolarization-activated, cyclic nucleotide-modulated pacemaker channels. J Pharmacol Exp Ther. 2007 Sep;322(3):931-939.

[Related Small Molecules]

ZD7288 | Zatebradine hydrochloride

Chemical & Physical Properties

[ Boiling Point ]:
655.7ºC at 760 mmHg

[ Molecular Formula ]:
C₂₈H₃₉ClN₂O₅

[ Molecular Weight ]:
519.07300

[ Flash Point ]:
350.4ºC

[ Exact Mass ]:
518.25500

[ PSA ]:
60.47000

[ LogP ]:
4.28070

[ Vapour Pressure ]:
1.96E-17mmHg at 25°C

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

Articles

Use-dependent blockade of cardiac pacemaker current (If) by cilobradine and zatebradine.

Eur. J. Pharmacol. 478 , 161-171, (2003)

The action of the bradycardiac agents, cilobradine (DK-AH269) and zatebradine (UL-FS49), on the cardiac pacemaker current (If) was investigated on short Purkinje fibres from sheep hearts, using the tw...

Bradycardic and proarrhythmic properties of sinus node inhibitors.

Mol. Pharmacol. 69 , 1328-1337, (2006)

Sinus node inhibitors reduce the heart rate presumably by blocking the pacemaker current If in the cardiac conduction system. This pacemaker current is carried by four hyperpolarization-activated, cyc...

Use-dependent block of Ih in mouse dorsal root ganglion neurons by sinus node inhibitors.

Br. J. Pharmacol. 125 , 741-750, (1998)

1. The sinus node inhibitors UL FS 49 and DK-AH 269 reduce heart rate by slowing diastolic depolarization rate in the sino-atrial (SA) node, which might originate from the use-dependent blockade of a ...