calcium channel (IC50 = 1 μM)
L-type calcium channels (cardiac). IC50 for inhibition of slow inward current (Isi) in frog atrial fibers: approximately 1 μM (concentration for half-maximal response) [1].
- Delayed potassium channels (nonspecific effect). At 10 μM, nicardipine substantially suppressed the delayed potassium current (IK) in frog atrial fibers [1].

Vascular smooth muscle cells' (VSMC) viability, proliferation, and ability to migrate are all decreased by nicarcine (0.1–10 μM; 24-48 hours) [2].

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In frog atrial fibers under voltage-clamp conditions, nicardipine (0.2-20 μM) inhibited the slow inward calcium current (Isi) in a concentration-dependent manner. The estimated IC50 for Isi block was approximately 1 μM. Nicardipine was about 5- to 10-fold less potent than nifedipine (IC50 ≈ 0.2 μM). Maximum block by nicardipine (at 20 μM, limited by solubility) reached about 70% of Isi (compared to 86% for nifedipine) [1].
- Nicardipine (1 μM) caused a tonic (resting) block of Isi of 65% ± 6% and an additional phasic (use-dependent) block of 35% ± 6% at a stimulation frequency of 0.2 Hz (total block 58% ± 7% at 1 Hz) [1].
- Nicardipine (1 μM) shifted the steady-state inactivation curve of Isi toward more negative potentials, indicating higher affinity for inactivated channels [1].
- When Ca²⁺ was replaced by Sr²⁺ (which slows inactivation), nicardipine (5 μM) not only reduced the peak Isi but also accelerated its decay. Similar effects were observed with Ba²⁺ or Na⁺ as charge carriers [1].
- Nicardipine (10 μM) substantially suppressed the delayed potassium current (IK) in frog atrial fibers (in the presence of Mn²⁺ to block Isi). This nonspecific effect occurred at concentrations similar to those inhibiting Isi [1].

Nicardipine (0.3–10 mg/kg) is an oral medication with antihypertensive effects [3]. Nicardipine's lethal dose (LD50) in male and female Sprague-Dawley rats is 643 mg/kg orally and 557 mg/kg orally; 18.1 mg/kg intravenously and 25.0 mg/kg intravenously; 735 mg/kg subcutaneously and 683 mg/kg kg subcutaneously; 171 mg/kg intraperitoneally and 155 mg/kg intraperitoneally [3]. Nicardipine's LD50 for male Wistar rats is 187 mg/kg when taken orally and 15.5 mg/kg when administered intravenously [3]. Nicardipine's lethal dose (LD50) for male and female mice is 634 mg/kg and 650 mg/kg, respectively; 20.7 mg/kg and 19.9 mg/kg, subcutaneous; 540 mg/kg and 710 mg/kg kg, subcutaneous; 144 mg/kg and 161 mg/kg, intraperitoneal [3].

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Cell Viability Assay[2]
Cell Types: VSMC isolated from New Zealand rabbit aorta preparation
Tested Concentrations: 0.1 μM, 1 μM, 3 μM, 10 μM
Incubation Duration: 24-48 hrs (hours)
Experimental Results: Treatment Dramatically diminished cell viability and inhibited VSMC proliferation in the presence of 10% FBS was in a dose-dependent manner, ranging from 205.4±17.5% to 176.6±17%, 160.6±5.7%, 150.4±11.2%, and 61.22±7.83% after 0.1 μM, 1 μM, 3 μM, and 10 μM, respectively. treat.

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Frog atrial fiber experiments: Atrial trabeculae (50-100 μm diameter, 3-4 mm length) isolated from frog heart (Rana esculenta) were used. The double sucrose gap technique was employed for voltage-clamp and current-clamp recordings. Fibers were continuously superfused with normal Ringer's solution (composition: NaCl 110.5 mM, CaCl₂ or SrCl₂ 1.8 mM, KCl 2.5 mM, MgCl₂ 2 mM, TRIS 3 mM, pH 7.4-7.6). Tetrodotoxin (1 μM) was used to suppress fast Na⁺ current. Nicardipine hydrochloride was first dissolved in water then diluted in Ringer's solution; concentrations above 20 μM could not be used due to precipitation. The test compartment was superfused at 1 mL/min; steady-state effect was measured after 3 min of drug exposure. Fibers were driven at 0.2 Hz (except where indicated). Tonic block was measured as percent inhibition at the first depolarization after 3 min of DHP perfusion without stimulation. Phasic block was evaluated after subsequent stimulation (steady-state after 1 min). Concentration-effect curves were cumulative, normalized between 0% and 100%, and reflected total block at 0.2 Hz stimulation. Maximum effect was determined by adding Mn²⁺ (5 mM) which fully inhibited Isi; the maximal block by nicardipine was 70% ± 5% (mean ± SEM, N=8) [1].
- Inactivation curve protocol: Conditioning pulses of 200 ms duration varied between -70 mV and +20 mV; test pulse was 0 mV amplitude, 100 ms duration; holding potential -70 mV; stimulation frequency 0.05 Hz. Steady-state inactivation curves were normalized to maximum current. Nicardipine (1 μM) shifted the curve to more negative potentials [1].

Animal/Disease Models: Conscious normotensive rat (NR)[3]
Doses: 0.3-10 mg/kg
Route of Administration: Oral
Experimental Results: Induced dose-dependent hypotensive response (maximum decrease in mean blood pressure, supine position) without any body positioning hypotensive reaction.

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Absorption, Distribution and Excretion
Nicardipine is completely absorbed, but its first-pass metabolism is saturated. At steady state, after oral administration of 30 mg, the systemic bioavailability is approximately 35%. Nicardipine has been shown to be rapidly and extensively metabolized in the liver. 8.3 L/kg 0.4 L/hr∙kg [Post-infusion] Metabolism/Metabolites Nicardipine hydrochloride is primarily metabolized in the liver. Known human metabolites of nicardipine include desbenzylidenepine and dehydronicardipine. Biological Half-Life 8.6 hours

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Hepatotoxicity
Even with long-term chronic treatment, nicardipine has not been shown to significantly increase the incidence of elevated serum transaminase or alkaline phosphatase levels. Although one case of significantly elevated serum enzymes without jaundice following intravenous nicardipine administration has been reported, there are no reported cases of specific liver injury. Large clinical trials of nicardipine have not mentioned liver injury, elevated serum transaminase levels, or discontinuation due to adverse liver events. Therefore, clinically significant liver injury with jaundice caused by nicardipine, even if it occurs, is certainly very rare. Probability score: E (Unlikely to be the cause of clinically significant liver injury). Some calcium channel blockers are known to cause specific liver injury, while others (such as nicardipine) do not; the reason for this is unclear.
Drug Category: Cardiovascular Drugs, Calcium Channel Blockers
Other Drugs in the Calcium Channel Blocker Subclass: Amlodipine, Diltiazem, Felodipine, Iradipine, Nifedipine, Nimodipine, Nisodipine, Verapamil
Pregnancy and Lactation Effects
◉ Overview of Use During Lactation
Due to the low concentration of nicardipine in breast milk, the amount ingested by the infant is very small, and no adverse effects are expected on breastfed infants. No special precautions are required.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.
Protein Binding
95%

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[1]. Electrophysiological analysis of the action of nifedipine and nicardipine on myocardial fibers. Fundam Clin Pharmacol. 1987;1(6):413-31.

[2]. The dihydropyridine calcium antagonist nicardipine reduces aortic smooth muscle cell viability, proliferation and migration. Cardiovascular Research, 2018 Apr,114(1):S43.

[3]. Sherrin H. Baky. Nic ardipine Hydrochloride.

Nicardipine is a racemic mixture composed of equimolar amounts of (R)-nicardipine and (S)-nicardipine. It is a calcium channel blocker used to treat hypertension. It has antihypertensive, calcium channel blocking, vasodilatory, and autophagy-inhibiting effects. It comprises (S)-nicardipine and (R)-nicardipine. Nicardipine is a dihydropyridine calcium channel blocker. Its mechanism of action is as a calcium channel antagonist, cytochrome P450 3A4 inhibitor, cytochrome P450 2D6 inhibitor, cytochrome P450 2C8 inhibitor, and cytochrome P450 2C19 inhibitor. Nicardipine is a second-generation calcium channel blocker used to treat hypertension and stable angina. Nicardipine treatment is associated with a low incidence of transient serum enzyme elevations, but there is no conclusive evidence that it is associated with clinically significant liver injury with jaundice.
Nicadipine is a synthetic derivative of nitrophenylpyridine and a potent calcium channel blocker. Nicardipine (a nifedipine-like drug) blocks the binding of calcium ions to certain cell walls, inhibiting the contraction of coronary and peripheral arteries, thereby reducing myocardial oxygen consumption and decreasing arterial constriction and spasm. Clinically, it is used as a cerebral and coronary artery vasodilator.
It is a potent calcium channel blocker with significant vasodilatory effects. It has antihypertensive properties and is effective in treating angina pectoris and coronary artery spasm without cardiac depressant effects. It is also used to treat asthma and can enhance the effects of certain antitumor drugs.
See also: Nicardipine hydrochloride (salt form).
Indications

For the treatment of patients with chronic stable angina and hypertension.

FDA Label
Mechanism of Action
Nicadipine inhibits the influx of extracellular calcium ions across the smooth muscle cell membranes of myocardial and vascular tissues by deforming ion channels, inhibiting ion-gating mechanisms, and/or interfering with calcium release from the sarcoplasmic reticulum. The decrease in intracellular calcium concentration inhibits the contractile process of myocardial smooth muscle cells, leading to dilation of coronary and systemic arteries, increasing oxygen delivery to myocardial tissue, reducing total peripheral resistance, lowering systemic blood pressure, and reducing afterload.
Pharmacodynamics
Nicadipine is a dihydropyridine calcium channel blocker that can be used alone or in combination with angiotensin-converting enzyme inhibitors for the treatment of hypertension, chronic stable angina, and Prinzmetal angina. Nicardipine is similar to other peripheral vasodilators. Nicardipine likely inhibits the influx of extracellular calcium ions across the smooth muscle cell membranes of myocardial and vascular tissues by deforming calcium channels, inhibiting ion-gating mechanisms, and/or interfering with calcium release from the sarcoplasmic reticulum. The decrease in intracellular calcium ion concentration inhibits the contraction process of myocardial smooth muscle cells, leading to dilation of coronary arteries and systemic arteries, increasing oxygen supply to myocardial tissue, reducing total peripheral resistance, lowering systemic blood pressure, and reducing afterload.

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Nicardipine is a dihydropyridine (DHP) calcium channel antagonist used in the treatment of cardiovascular disorders. It has a pKa of 7.0 (partially ionized at normal pH), whereas nifedipine is neutral (pKa ≈ 1.0) [1].
- Unlike nifedipine, nicardipine is not photolabile; a single UV flash did not reverse its blockade of calcium channels [1].
- The mechanism of nicardipine action on calcium channels can be described by the "modulated receptor hypothesis": it binds to closed, open, and inactivated states of the channel, with higher affinity for inactivated channels. This is supported by the shift of inactivation curves and the enhanced block at depolarized holding potentials (e.g., from 40% inhibition at -70 mV to 60% at -30 mV for 1 μM nicardipine) [1].
- In vascular smooth muscle, nicardipine is reported to be a very potent calcium antagonist (reference cited). Its higher specificity for smooth muscle calcium channels may explain its less negative inotropic effect on cardiac muscle at a given concentration, consistent with in vivo observations in anesthetized dogs (referenced) [1].

C26H29N3O6

479.525

479.206

C, 65.12; H, 6.10; N, 8.76; O, 20.02

55985-32-5

Nicardipine hydrochloride;54527-84-3;Nicardipine-d3 hydrochloride;1432061-50-1;(S)-Nicardipine;76093-36-2;(R)-Nicardipine;76093-35-1

4474

Typically exists as light yellow to yellow solids at room temperature

1.23 g/cm3

603.4ºC at 760 mmHg

136-138ºC

318.7ºC

4.529

1

8

10

35

856

0

O=C(C1=C(C)NC(C)=C(C(OCCN(C)CC2=CC=CC=C2)=O)C1C3=CC=CC([N+]([O-])=O)=C3)OC

ZBBHBTPTTSWHBA-UHFFFAOYSA-N

InChI=1S/C26H29N3O6/c1-17-22(25(30)34-4)24(20-11-8-12-21(15-20)29(32)33)23(18(2)27-17)26(31)35-14-13-28(3)16-19-9-6-5-7-10-19/h5-12,15,24,27H,13-14,16H2,1-4H3

3-(2-(benzyl(methyl)amino)ethyl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

DaganFlusemide; Nicardipine; Cardene; nicardipine; 55985-32-5; Nicardipinum; Nicardipino; Perpidine; Nicardipinum [INN-Latin]; Nicardipino [INN-Spanish]; Nicardipine (stn);Antagonil

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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