Ivabradine Hydrochloride is a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide-gated channels, inducing heart rate (HR) reduction[3]. Ivabradine at 10 mg/kg/day reduced the maximal HR increase in response to the β-agonist isoproterenol, without modifying the response of contractile parameters [4]. Ivabradine induced a time-dependent inhibition of hHCN4 with an IC50 of 0.5 μM. Ivabradine 3 μM decreased the frequency of action potentials in SAN (sino-atrial nodes) from guinea-pig, rabbit and pig by 33%, 21% and 15% at 40 min, respectively[5].
Ivabradine HCl/盐酸伊伐布雷定 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MCF-10A
5 µM
2 weeks
Clin Transl Med. 2021 Nov;11(11):e578.
MDA-MB-453
5 µM
2 weeks
Suppressed cell proliferation
Clin Transl Med. 2021 Nov;11(11):e578.
MDA-MB-231
5 µM
2 weeks
Suppressed cell proliferation
Clin Transl Med. 2021 Nov;11(11):e578.
SAN myocytes
1 µM
To evaluate the effect of Ivabradine on the spontaneous beating rate of SAN cells, results showed Ivabradine reduced the beating rate in control cells but had no effect on mutant cells.
Nat Commun. 2014 Aug 21;5:4664.
HEK293 cells
30 μM
Assess the current properties of HCN4 channels under AP clamp
Proc Natl Acad Sci U S A. 2021 Jul 13;118(28):e2104668118.
Murine sinoatrial node myocytes
30 μM
120 seconds
Evaluate the blocking effect of ivabradine on If current
Proc Natl Acad Sci U S A. 2021 Jul 13;118(28):e2104668118.
SAN pacemaker cells
3 or 10 µM
To evaluate the inhibitory effect of Ivabradine on If current in SAN cells, showing similar inhibition in both control and mutant groups.
Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12189-94.
Ivabradine HCl/盐酸伊伐布雷定 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Type 1 and Type 2 diabetes models
Intraperitoneal injection
2.5 mg/kg, 5 mg/kg, 10 mg/kg
Single or multiple injections
Ivabradine significantly reversed mechanical hypersensitivity in diabetic mice in a dose-dependent manner. Multiple injections completely restored pain thresholds to pre-diabetic levels.
Sci Transl Med. 2017 Sep 27;9(409):eaam6072
Mice
Diabetic mouse model
Oral
20 mg/kg/day
Once daily for 4 weeks
To investigate the effect of selective heart rate reduction on cardiovascular function and ventricular-arterial coupling in a diabetic mouse model. Results showed that Ivabradine improved vascular stiffness and left ventricular systolic and diastolic function.
Eur Heart J. 2013 Sep;34(36):2839-49
Mice
Swim training model
Oral
7.5 mg
Single dose
To assess the effect of Ivabradine on heart rate
Circ Res. 2017 Oct 13;121(9):1058-1068
Mice
Ncx1−/− mice
30 µM
To investigate the effect of Ivabradine on the automaticity of SAN cells in Ncx1?/? mice, results showed that under basal conditions, Ivabradine similarly reduced SAN cell automaticity in both Ncx1?/? and control mice; however, after isoproterenol stimulation, SAN cells from Ncx1?/? mice were significantly more sensitive to Ivabradine
Circ Res. 2013 Jan 18;112(2):309-17
Mice
HHCN4-AYA transgenic mice
Intraperitoneal injection
6 mg/kg
Single dose
To evaluate the effect of Ivabradine on heart rate, results showed Ivabradine reduced heart rate in control mice but had no effect on mutant mice.
Nat Commun. 2014 Aug 21;5:4664.
Mice
Cardiac-specific TRPM7 knockout mice
3 mg/kg and 6 mg/kg
KOαMHC-Cre mice were less sensitive to the negative chronotropic effects of ivabradine compared to wild-type mice
Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):E3037-46
Mice
Atrial-specific NCX knockout mice
Perfusion
3 μM
Suppressed NCX KO SAN automaticity, reducing burst firing activity
Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9769-74
Nude mice
MDA-MB-231 xenograft model
Subcutaneous injection
15 mg/kg
Once daily for 4 weeks
Significantly reduced tumor volume
Clin Transl Med. 2021 Nov;11(11):e578.
Mice
Conditional hHCN4–573X transgenic mice
Intraperitoneal injection
3 or 6 mg/kg
Single dose, observed for 3 hours
To assess the effect of Ivabradine on heart rate, showing significant reduction in controls but no effect in mutants.
Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12189-94.
Mice
Oxaliplatin-induced cold hypersensitivity model
Intraperitoneal injection
3 mg/kg
Single injection
To evaluate the effect of ivabradine on oxaliplatin-induced cold hypersensitivity, it was found that ivabradine significantly alleviated cold hypersensitivity
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