54527-84-3

Basic information

• Product Name: Nicardipine hydrochloride
• Synonyms: 2-(benzylmethylamino)ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylatemonohydrochloride;Naratriptan HCl;NICARDIPINE HYDROCHLORIDE (YC-93) CALCIU M CHANNEL ANTAG;NICARDIPINE HYDROCHLORIDE MM(CRM STANDARD);1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic Acid Methyl 2-[Methyl(phenylmethyl)amino]ethyl Ester Hydrochloride;Antagonyl;Barizin;Dacarel
• CAS NO: 54527-84-3
• Molecular Formula: C₂₆H₂₉N₃O₆*ClH
• Molecular Weight: 515.99
• EINECS: 259-198-4
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Calcium channel;TRONOLANE;Cardiovascular APIs
• Mol File: 54527-84-3.mol
• Article Data: 9

Chemical Properties

• Melting Point: 176-1780C
• Boiling Point: 603.4 °C at 760 mmHg
• Flash Point: 318.7 °C
• Appearance: yellow/powder
• Vapor Pressure: 1.63E-14mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: DMSO: ~1 mg/mL
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in distilled water or ethanol may be stored at -20°C for up to 1 month.
• Merck: 14,6495
• CAS DataBase Reference: Nicardipine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Nicardipine hydrochloride(54527-84-3)
• EPA Substance Registry System: Nicardipine hydrochloride(54527-84-3)

Safety Data

• Hazard Codes: T
• Statements: 23/24/25
• Safety Statements: 36/37/39-45
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: US7972100
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 54527-84-3(Hazardous Substances Data)

Usage

Description

Nicardipine is a dihydropyridine L-type calcium channel antagonist that displays antihypertensive and antianginal activity. It is reported to inhibit adenosine A1, A2A, and A3 receptors with Ki values of 19.6, 63.8, and 3.25 μM, respectively, and can inhibit cytochrome P450 3A4 catalytic activity with an IC50 value of 0.148 μM. Additionally, nicardipine has been shown to activate transient receptor potential A1 channels, producing an increase in Ca2+ (EC50 = 0.5 μM).

Chemical Properties

Yellow Solid

Uses

Different sources of media describe the Uses of 54527-84-3 differently. You can refer to the following data:
1. anesthetic (topical)
2. Nicardipine is a dihydropyridine L-type calcium channel antagonist that displays antihypertensive and antianginal activity. It is reported to inhibit adenosine A1, A2A, and A3 receptors with Ki values of 19.6, 63.8, and 3.25 μM, respectively, and can inhibit cytochrome P450 3A4 catalytic activity with an IC50 value of 0.148 μM. Additionally, nicardipine has been shown to activate transient receptor potential A1 channels, producing an increase in Ca2+ (EC50 = 0.5 μM).

Brand name

Cardene(PDL Biopharma); Cardene (Roche).

General Description

Nicardipine hydrochloride,1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylicacid methyl 2-[methyl(phenylmethyl)amino]ethylester hydrochloride (Cardene), is a more potent vasodilator ofthe systemic, coronary, cerebral, and renal vasculature andhas been used in the treatment of mild, moderate, and severehypertension. The drug is also used in the management of stableangina.

Biochem/physiol Actions

Blocks L-type voltage-dependent calcium channels; antihypertensive.

Clinical Use

Calcium-channel blocker: Prophylaxis and treatment of angina Mild to moderate hypertension Acute life-threatening hypertension and post operative hypertension (IV)

Safety Profile

Poison by ingestion, intravenous, and intraperitoneal routes. Moderately toxic by subcutaneous route. Human systemic effects: decreased urine volume or anuria. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of NOx an

Drug interactions

Potentially hazardous interactions with other drugs Aminophylline: possibly increases aminophylline concentration. Anaesthetics: enhanced hypotensive effect. Antibacterials: metabolism possibly accelerated by rifampicin; metabolism possibly inhibited by clarithromycin, erythromycin and telithromycin. Antidepressants: enhanced hypotensive effect with MAOIs. Antiepileptics: effect reduced by carbamazepine, barbiturates, phenytoin and primidone. Antifungals: metabolism possibly inhibited by itraconazole and ketoconazole; negative inotropic effect possibly increased with itraconazole. Antihypertensives: enhanced hypotensive effect, increased risk of first dose hypotensive effect of post synaptic alpha-blockers. Antivirals: concentration possibly increased by ritonavir; use telaprevir with caution. Cardiac glycosides: digoxin concentration increased. Ciclosporin: concentration of ciclosporin increased Grapefruit juice: concentration increased - avoid. Tacrolimus: may increase tacrolimus levels. Theophylline: possibly increased theophylline concentration.

Metabolism

Nicardipine is subject to saturable first-pass metabolism. It is extensively metabolised in the liver and excreted in the urine and faeces, mainly as inactive metabolites.

References

1) Merck 14 6495 2) Hulubei et al. (2012), 4-Isoxazolyl-1,4-dihydropyridines exhibit binding at the multidrug-resistance transporter; Bioorg. Med. Chem., 20 6620

InChI:InChI=1/C26H29N3O6.ClH/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;1H

Upstream product

• 99-61-6 3-nitro-benzaldehyde 
• 14205-39-1 methyl 3-aminocrotonate 
• 101-98-4 2-(N-benzyl-N-methyl)amino-1-ethanol 
• 54527-65-0 acetoacetic acid [2-(N-methyl-N-benzylamino)-ethyl]-ester 
• 14205-39-1 methyl (E)-3-aminocrotonate 
• 39562-17-9 methyl 2-(3-nitrophenylmethylene)acetoacetate 
• 54527-73-0 2-(N-benzyl-N-methylamino)-ethyl 3-aminocrotonate 
• 85677-95-8 2-hydroxyethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate 
• 103785-47-3 methanesulfonyloxyethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate 
• 103-67-3 benzyl-methyl-amine 

Downstream Products

• 101-98-4 2-(N-benzyl-N-methyl)amino-1-ethanol 
• 1259327-68-8 C₁₆H₁₅N₂O₆^(1-)*Na⁽¹⁺⁾ 
• 69441-29-8 2,6-Dimethyl-4-(3-nitro-phenyl)-pyridine-3,5-dicarboxylic acid 3-[2-(benzyl-methyl-amino)-ethyl] ester 5-methyl ester; hydrochloride 

Relevant articles and documents

METHODS FOR TREATING CHRONIC FATIGUE SYNDROME AND MYALGIC ENCEPHALOMYELITIS

In one aspect the invention relates to a method of treatment selected from the group consisting of: (a) treating a symptom such as pain in a subject identified or diagnosed as having Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); (b) treating a symptom such as pain in a subject having dysfunctional TRPM3 ion channel activity; (c) restoring NK cell function in a subject having dysfunctional TRPM3 ion channel activity; and (d) restoring calcium homeostasis in a subject having dysfunctional TRPM3 ion channel activity. The method comprises the step of administering to the subject a therapeutically effective amount of at least one therapeutic compound selected from the group consisting of: (i) an opioid receptor antagonist; (ii) an opioid antagonist; and (iii) a therapeutic compound that restores TRPM3 ion channel activity. In some embodiments the therapeutic compound is naltrexone hydrochloride.

Processes of manufacturing substituted-1,4-dihydropyridines, improved aqueous solutions thereof, and processes of manufacturing the solutions

A process of preparing a stable parenteral solution of a 1,4-dihydropyridine salt, such as nicardipine hydrochloride, in an acidic aqueous medium. The presence of L-arginine in the solution enhances the solubility of the salt, which is poorly soluble in water. An aqueous, injectable isotonic solution at pH about 3.5-3.6 consists essentially of nicardipine hydrochloride, L-arginine, and a sugar alcohol. An improved single pot manufacturing process for obtaining unsymmetrical 1,4-dihydropyridines by using more than one mole equivalent of aldehyde with respect to the other reactants (amino crotonate and acetoacetate ester). The reaction can be conducted in a solvent present at 20 times the amount of any one component. A process for changing one polymorph of nicardipine hydrochloride (Form A) into another (Form B), and a separate process for the reverse (Form B into Form A).

Inclusion complex of nicardipine or its hydrochloride with beta-cyclodextrin, a process for preparing the same and a sustained release pharmaceutical preparation containing the same

There is described a new inclusion complex of nicardipine or its hydrochloride with beta-cyclodextrin, which is prepared by admixing nicardipine or its hydrochloride with beta--cyclodextrin in a molar ratio of the compounds 1:0.9-1.1 under stirring at a temperature from about room temperature to the boiling temprature of the reaction mixture in an aqueous or ethanolic medium, cooling the reaction mixture to 0 ° to 5 °C and isolating the desired complex. The inclusion complex of nicardipine or its hydrochloride pos-sesses cerebrovascular-vasodilatory and coronary-vasodilatory properties, which are equally well expressed as those of nicar-dipine or its hydrochloride themselves, yet owing to the better solubility of the complex at a higher pH range, such as it ex-ists e.g. in the intestinal tract, the manufacture of sustained release pharmaceutical forms is made possible, whereby a greater extent of dissolution of the active substance is provided also in the intestinal juice.