calcium channel (IC50 = 1 μM)

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

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].

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.

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.

Absorption, Distribution and Excretion
While nicardipine is completely absorbed, it is subject to saturable first pass metabolism and the systemic bioavailability is about 35% following a 30 mg oral dose at steady state.
Nicardipine has been shown to be rapidly and extensively metabolized by the liver.
8.3 L/kg
0.4 L/hr∙kg [Following infusion]

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Metabolism / Metabolites
Nicardipine HCl is metabolized extensively by the liver.
Nicardipine has known human metabolites that include De-benzylated nicardipine and Dehydronicardipine.

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Biological Half-Life
8.6 hours

Hepatotoxicity
Nicardipine has not been associated with significant increases in rates of elevations in serum aminotransferase or alkaline phosphatase levels, even with chronic long term therapy. Cases of idiosyncratic liver injury have not been published, although a single instance of marked serum enzyme elevations without jaundice has been reported with the use of intravenous nicardipine. Large trials of nicardipine have not mentioned liver injury, serum aminotransferase elevations or discontinuation of drug because of hepatic adverse events. Thus, clinically apparent liver injury with jaundice due to nicardipine must be rare, if it occurs at all.
Likelihood Score: E (unlikely cause of clinically apparent liver injury).
The reason why some calcium channel blockers are known to cause idiosyncratic liver injury while others such as nicardipine do not, is unknown.
Drug Class: Cardiovascular Agents, Calcium Channel Blockers
Other Drugs in the Subclass, Calcium Channel Blockers: Amlodipine, Diltiazem, Felodipine, Isradipine, Nifedipine, Nimodipine, Nisoldipine, Verapamil

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because of the low levels of nicardipine in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. No special precautions are required.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
>95%

[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 racemate comprising equimolar amounts of (R)- and (S)-nicardipine. It is a calcium channel blocker which is used to treat hypertension. It has a role as an antihypertensive agent, a calcium channel blocker, a vasodilator agent and an autophagy inhibitor. It contains a (S)-nicardipine and a (R)-nicardipine.
Nicardipine is a Dihydropyridine Calcium Channel Blocker. The mechanism of action of nicardipine is as a Calcium Channel Antagonist, and Cytochrome P450 3A4 Inhibitor, and Cytochrome P450 2D6 Inhibitor, and Cytochrome P450 2C8 Inhibitor, and Cytochrome P450 2C19 Inhibitor.
Nicardipine is a second generation calcium channel blocker used in the treatment of hypertension and stable angina pectoris. Nicardipene therapy has been associated with a low rate of transient serum enzyme elevations, but has not been linked convincingly to instances of clinically apparent liver injury with jaundice.
Nicardipine is a synthetic derivative of nitrophenyl-pyridine and potent calcium channel blocker, Nicardipine (Nifedipine Family) blocks calcium ions from certain cell walls and inhibits contraction of coronary and peripheral arteries, resulting in lowered oxygen requirements for heart muscle and decreased arterial contraction and spasm. It is used clinically as a cerebral and coronary vasodilator.
A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents.
See also: Nicardipine Hydrochloride (has salt form).

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Drug Indication
Used for the management of patients with chronic stable angina and for the treatment of hypertension.
FDA Label

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Mechanism of Action
By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, nicardipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

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Pharmacodynamics
Nicardipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nicardipine is similar to other peripheral vasodilators. Nicardipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

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.)