Adrenergic Receptor

Ivabradine hydrochloride (1, 10, 20 mg/kg; i.p.) exhibits anticonvulsant and neuroprotective properties in mice[3]. Ivabradine hydrochloride (5, 10, 20 mg/kg;p.o.; daily for 1 weeks) reduces heart rate in mice with increased sympathoadrenergic activity[4].

[1]. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005 Dec;26(23):2529-36.

[2]. Heart rate slowing for myocardial dysfunction/heart failure. Adv Cardiol. 2006;43:97-105.

[3]. Ivabradine possesses anticonvulsant and neuroprotective action in mice. Biomed Pharmacother. 2019 Jan;109:2499-2512.

[4]. I(f) channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities. Br J Pharmacol. 2004 May;142(1):107-12.

Ivabradine hydrochloride is a hydrochloride obtained by combining ivabradine with one molar equivalent of hydrochloric acid. Used to treat patients with angina who have intolerance to beta blockers and/or heart failure. It has a role as a cardiotonic drug. It contains an ivabradine(1+).
Ivabradine Hydrochloride is the hydrochloride salt form of ivabradine, an orally bioavailable, hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel blocker, with negative chronotropic activity. Upon administration, ivabradine selectively binds to the intracellular portion of the HCN channel pore and blocks HCN channels in the pacemaker cells within the sinoatrial (SA) node. This inhibits the If (funny) pacemaker ion current, prevents the inward flow and intracellular accumulation of positively charged ions, reduces pacemaker activity and slows diastolic depolarization. This decreases heart rate, reduces myocardial oxygen demand and allows more time for blood to flow to the myocardium without affecting cardiac contractility. HCN channels, mixed sodium (Na+) and potassium (K+) channels that carry the inward If current, play a key role in the regulation of pacemaker firing rate in the SA node. The If pacemaker current, the inward flow of positively charged Na+-K+ ions, initiates the spontaneous diastolic depolarization phase and modulating heart rate.
A benzazepine derivative and selective HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED CHANNELS inhibitor that lowers the heart rate. It is used in the treatment of CHRONIC STABLE ANGINA in patients unable to take BETA-ADRENERGIC BLOCKERS, and in the treatment of HEART FAILURE.
See also: Ivabradine (has active moiety).

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Drug Indication
Symptomatic treatment of chronic stable angina pectoris Ivabradine is indicated for the symptomatic treatment of chronic stable angina pectoris in coronary artery disease adults with normal sinus rhythm and heart rate ≥ 70 bpm. Ivabradine is indicated: in adults unable to tolerate or with a contra-indication to the use of beta-blockersorin combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose. Treatment of chronic heart failure Ivabradine is indicated in chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is ≥ 75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated.
Symptomatic treatment of chronic stable angina pectorisIvabradine is indicated for the symptomatic treatment of chronic stable angina pectoris in coronary artery disease adults with normal sinus rhythm and heart rate ≥ 70 bpm. Ivabradine is indicated : - in adults unable to tolerate or with a contra-indication to the use of beta-blockers- or in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose. Treatment of chronic heart failureIvabradine is indicated in chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is ≥ 75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated. (see section 5. 1)
Symptomatic treatment of chronic stable angina pectorisIvabradine is indicated for the symptomatic treatment of chronic stable angina pectoris in coronary artery disease adults with normal sinus rhythm and heart rate ≥ 70 bpm. Ivabradine is indicated: in adults unable to tolerate or with a contraindication to the use of beta-blockersor in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose. Treatment of chronic heart failureIvabradine is indicated in chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is ≥ 75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated.
Symptomatic treatment of chronic stable angina pectoris Ivabradine is indicated for the symptomatic treatment of chronic stable angina pectoris in coronary artery disease adults with normal sinus rhythm and heart rate ≥ 70 bpm. Ivabradine is indicated : in adults unable to tolerate or with a contraindication to the use of beta-blockersor in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose. Treatment of chronic heart failure Ivabradine is indicated in chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is ≥ 75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated.
Symptomatic treatment of chronic stable angina pectoris in coronary artery disease adults with normal sinus rhythm and heart rate ≥ 70 bpm. Ivabradine is indicated: - in adults unable to tolerate or with a contra-indication to the use of beta-blockers - or in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose. Treatment of chronic heart failure Ivabradine is indicated in chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is ≥ 75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated. ,
Treatment of angina pectoris, Treatment of chronic heart failure, Treatment of coronary artery disease
Treatment of angina pectoris, Treatment of chronic heart failure, Treatment of coronary artery disease

C27H37CLN2O5

505.05

504.239

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

148849-67-6

Ivabradine metabolite N-Demethyl Ivabradine hydrochloride; 1246638-08-3; Ivabradine-d6 hydrochloride; 2070009-63-9; Ivabradine; 155974-00-8; Ivabradine-d3 hydrochloride; 1217809-61-4; Ivabradine-d6; 1202000-62-1 (sulfate); 1086026-42-7 (oxalate); 1422274-66-5 (hemisulfate)

3045381

White to off-white solid powder

626.9ºC at 760mmHg

193-196?C

332.9ºC

1.24E-15mmHg at 25°C

4.049

1

6

10

35

663

1

Cl[H].O(C([H])([H])[H])C1=C(C([H])=C2C(=C1[H])[C@@]([H])(C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])N1C(C([H])([H])C3=C([H])C(=C(C([H])=C3C([H])([H])C1([H])[H])OC([H])([H])[H])OC([H])([H])[H])=O)C2([H])[H])OC([H])([H])[H]

HLUKNZUABFFNQS-ZMBIFBSDSA-N

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

3-[3-[[(7S)-3,4-dimethoxy-7-bicyclo[4.2.0]octa-1,3,5-trienyl]methyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: 50 mg/mL (99.00 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)