Ivabradine HCl | CAS#148849-67-6 | 1202000-62-1 | 155974-00-8 | funny channel inhibitor

MedKoo Cat#: 317108 | Name: Ivabradine HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ivabradine is a novel medication used for the symptomatic management of stable angina pectoris. Ivabradine acts by reducing the heart rate via specific inhibition of the funny channel, a mechanism different from that of beta blockers and calcium channel blockers, two commonly prescribed antianginal drugs. Ivabradine is a cardiotonic agent. Ivabradine was approved in 2015. Ivabradine acts on the If (f is for "funny", so called because it had unusual properties compared with other current systems known at the time of its discovery) ion current, which is highly expressed in the sinoatrial node. If is a mixed Na+–K+ inward current activated by hyperpolarization and modulated by the autonomic nervous system. It is one of the most important ionic currents for regulating pacemaker activity in the sinoatrial (SA) node. Ivabradine selectively inhibits the pacemaker If current in a dose-dependent manner. Blocking this channel reduces cardiac pacemaker activity, slowing the heart rate and allowing more time for blood to flow to the myocardium.

Chemical Structure

Ivabradine HCl

CAS#148849-67-6 (HCl)

Theoretical Analysis

MedKoo Cat#: 317108

Name: Ivabradine HCl

CAS#: 148849-67-6 (HCl)

Chemical Formula: C27H37ClN2O5

Exact Mass: 0.0000

Molecular Weight: 505.05

Elemental Analysis: C, 64.21; H, 7.38; Cl, 7.02; N, 5.55; O, 15.84

Price and Availability

Size	Price	Availability
50mg	USD 190.00	Ready to ship
100mg	USD 350.00	Ready to ship
200mg	USD 650.00	Ready to ship
500mg	USD 1,250.00	Ready to ship
1g	USD 1,550.00	Ready to ship
2g	USD 2,250.00	Ready to ship
5g	USD 2,950.00	Ready to ship
10g	USD 3,650.00	Ready to ship

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Related CAS #

155974-00-8 (free base) 1202000-62-1 (sulfate) 148849-67-6 (HCl) 1086026-42-7 (oxalate) 1422274-66-5 (hemisulfate)

Synonym

S16257; S 16257; S-16257; S 16257-2; S-16257-2; S16257-2; Ivabradine HCl; Corlentor; Procoralan; Coralan; Coraxan; Ivabid; Bradia.

IUPAC/Chemical Name

(S)-3-(3-(((3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)methyl)(methyl)amino)propyl)-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzo[d]azepin-2-one hydrochloride

InChi Key

HLUKNZUABFFNQS-ZMBIFBSDSA-N

InChi Code

InChI=1S/C27H36N2O5.ClH/c1-28(17-21-11-20-14-25(33-4)26(34-5)16-22(20)21)8-6-9-29-10-7-18-12-23(31-2)24(32-3)13-19(18)15-27(29)30;/h12-14,16,21H,6-11,15,17H2,1-5H3;1H/t21-;/m1./s1

SMILES Code

O=C1N(CCCN(C[C@@H]2C3=CC(OC)=C(OC)C=C3C2)C)CCC4=CC(OC)=C(OC)C=C4C1.[H]Cl

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Related CAS# 155974-00-8 (Ivabradine) 1202000-62-1 (Ivabradine sulfate) 148849-67-6 (Ivabradine hydrochloride)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#X7P07R21

QC Data

View QC data: current batch, Lot#X7P07R21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ivabradine hydrochloride is an orally bioavailable, hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel blocker.

In vitro activity:

Ivabradine treatment significantly reduced If at membrane potentials from − 90 to − 130 mV in both S-LPS- and R595-incubated cardiomyocytes (Figs. 6A and B). The significantly reduced If current density at a membrane potential of − 80 mV in R595 incubated cells (Fig. 6B) did not differ from current rundown (Fig. 6D). Fig. 6C shows the time-dependent development of ivabradine induced If blockage in control and S-LPS/R595 incubated cells at a membrane potential of − 100 mV (protocol p2, see inset Fig. 5A). If blockage by ivabradine was significantly higher in controls than in endotoxin incubated cells but did not differ between the two LPS forms. Furthermore, current rundown in control cardiomyocytes (beginning 2.5 min after protocol p2 had been started) was significantly smaller than If reduction in all ivabradine-treated cardiomyocytes. Reference: J Mol Cell Cardiol. 2014 Jul; 72(100): 64–73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046244/

In vivo activity:

As shown in Figure 2A, in animals pretreated with 5 mg/kg ELA (Ivabradine), oral administration of 20 and 30 (but not 10) mg/kg IVA markedly reduced spontaneous ASs, an effect that for the highest dose was visible as early as 20 min after IVA administration and lasted for the entire duration of the recorded period (2 h). Statistical analysis of the normalized AUC of the entire test period showed a significant reduction (62%) of the total time spent in seizures for the ELA + IVA30 group (.38 ± .09, F = 8.77, DFn = 5, DFd = 22, p = .0044), but not for the ELA + IVA20 (.53 ± .09, p = .07), ELA + IVA10 (1.05 ± .09, p > .99), ELA + VEH2 (1.2 ± .16, p = .61), and VEH1 + IVA groups (1.12 ± .11, p = .86) compared to VEH1 + VEH2 (Figure 2B1). The mean duration of the seizures was also significantly decreased (F = 6.67, DFn = 5, DFd = 22, 41%) in the ELA + IVA30 group (.59 ± .07, p = .008), but not in the ELA + IVA20 (.66 ± .09, p = .09), ELA + IVA10 (1.03 ± .1, p > .99), ELA + VEH2 (1.06 ± .08, p > .99), and VEH1 + IVA groups (1.06 ± .09, p = .95) compared to VEH1 + VEH2 (Figure 2B2). Moreover, the number of seizures showed a significant decrease (45%) in rats treated with ELA + IVA30 (.55 ± .09, F = 4.35, DFn = 5, DFd = 46, p = .01) but not in the ELA + IVA20 (.71 ± .09, p = .24), ELA + IVA10 (.99 ± .09, p > .99), ELA + VEH2 (1.08 ± .13, p = .98), and VEH1 + IVA groups (1.03 ± .06, p = .99) compared to VEH1 + VEH2 (Figure 2B3). Reference: Epilepsia. 2021 May 20. doi: 10.1111/epi.16926. https://onlinelibrary.wiley.com/doi/10.1111/epi.16926

	Solvent	mg/mL	mM
Solubility
	DMSO	48.9	96.78
	DMF	25.0	49.50
	Ethanol	55.0	108.90
	PBS (pH 7.2)	10.0	19.80
	Water	66.8	132.34

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 505.05 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Haechl N, Ebner J, Hilber K, Todt H, Koenig X. Pharmacological Profile of the Bradycardic Agent Ivabradine on Human Cardiac Ion Channels. Cell Physiol Biochem. 2019;53(1):36-48. doi: 10.33594/000000119. PMID: 31169990. 2. Scheruebel S, Koyani CN, Hallström S, Lang P, Platzer D, Mächler H, Lohner K, Malle E, Zorn-Pauly K, Pelzmann B. I(f) blocking potency of ivabradine is preserved under elevated endotoxin levels in human atrial myocytes. J Mol Cell Cardiol. 2014 Jul;72(100):64-73. doi: 10.1016/j.yjmcc.2014.02.010. Epub 2014 Feb 25. PMID: 24583250; PMCID: PMC4046244. 3. Iacone Y, Morais TP, David F, Delicata F, Sandle J, Raffai T, Parri HR, Weisser JJ, Bundgaard C, Klewe IV, Tamás G, Thomsen MS, Crunelli V, Lőrincz ML. Systemic administration of ivabradine, a hyperpolarization-activated cyclic nucleotide-gated channel inhibitor, blocks spontaneous absence seizures. Epilepsia. 2021 May 20. doi: 10.1111/epi.16926. Epub ahead of print. PMID: 34018186. 4. Scridon A, Halaţiu VB, Balan AI, Cozac DA, Moldovan V, Bănescu C, Perian M, Şerban RC. Long-Term Effects of Ivabradine on Cardiac Vagal Parasympathetic Function in Normal Rats. Front Pharmacol. 2021 Apr 8;12:596956. doi: 10.3389/fphar.2021.596956. PMID: 33897414; PMCID: PMC8061748.

In vitro protocol:

In vivo protocol:

1. Iacone Y, Morais TP, David F, Delicata F, Sandle J, Raffai T, Parri HR, Weisser JJ, Bundgaard C, Klewe IV, Tamás G, Thomsen MS, Crunelli V, Lőrincz ML. Systemic administration of ivabradine, a hyperpolarization-activated cyclic nucleotide-gated channel inhibitor, blocks spontaneous absence seizures. Epilepsia. 2021 May 20. doi: 10.1111/epi.16926. Epub ahead of print. PMID: 34018186. 2. Scridon A, Halaţiu VB, Balan AI, Cozac DA, Moldovan V, Bănescu C, Perian M, Şerban RC. Long-Term Effects of Ivabradine on Cardiac Vagal Parasympathetic Function in Normal Rats. Front Pharmacol. 2021 Apr 8;12:596956. doi: 10.3389/fphar.2021.596956. PMID: 33897414; PMCID: PMC8061748.

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