Nilvadipine (formerly ARC-029; FR34235, FK235; ARC029; FR-34235; FK-235; Escor, Nivadil) is a potent calcium channel blocker (CCB) with potential antihypertensive activity. It has been used to treat chronic major cerebral artery occlusion and hypertension. Its IC50 is 0.03 NM, which indicates that it inhibits the calcium channel. In rat aortic smooth muscle cells (SMC), nilvadipine exhibits a strong chemotaxis-inhibiting effect on interleukin-1 (IL-1), leukotriene B4 (LTB4), and platelet-derived growth factor (PDGF), with an IC50 of 0.1 nM. It has been observed that nilvadipine increases renal blood flow and decreases the filtration fraction in the isolated perfused kidney of a hydronephrotic patient, which may indicate afferent and efferent arteriolar vasodilation indirectly.

Physicochemical Properties

Molecular Formula	C19H19N3O6
Molecular Weight	385.37
Exact Mass	385.127
Elemental Analysis	C, 59.22; H, 4.97; N, 10.90; O, 24.91
CAS #	75530-68-6
Related CAS #	Nilvadipine-d4
PubChem CID	4494
Appearance	Light yellow to green yellow solid powder
Density	1.3±0.1 g/cm3
Boiling Point	526.7±50.0 °C at 760 mmHg
Melting Point	148-150ºC
Flash Point	272.3±30.1 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.584
LogP	1.72
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	6
Heavy Atom Count	28
Complexity	783
Defined Atom Stereocenter Count	0
SMILES	O(C([H])(C([H])([H])[H])C([H])([H])[H])C(C1=C(C([H])([H])[H])N([H])C(C#N)=C(C(=O)OC([H])([H])[H])C1([H])C1C([H])=C([H])C([H])=C(C=1[H])[N+](=O)[O-])=O
InChi Key	FAIIFDPAEUKBEP-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H19N3O6/c1-10(2)28-19(24)15-11(3)21-14(9-20)17(18(23)27-4)16(15)12-6-5-7-13(8-12)22(25)26/h5-8,10,16,21H,1-4H3
Chemical Name	3-O-methyl 5-O-propan-2-yl 2-cyano-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Synonyms	ARC029; FR34235; Escor; Nivadil; FR-34235, FK-235;FR 34235; FK 235; ARC-029; ARC 029; FR34235; FK235
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Calcium channel ( IC50 = 0.1 nM )
ln Vitro	In vitro activity: Nilvadipine has an IC50 of 0.1 nM and significantly inhibits the chemotaxis of platelet-derived growth factor (PDGF), leukotriene B4 (LTB4), and interleukin-1 (IL-1). This was observed in rat aortic smooth muscle cells (SMC). [1] In the isolated perfused hydronephrotic kidney, nilvadipine is reported to increase renal blood flow and decrease the filtration fraction, implying indirect afferent and efferent arteriolar vasodilation. [2]
ln Vivo	Nilvadipine retains electroretinogram responses and retinal morphology in RCS rats during the early stages of retinal degeneration. In the retina of RCS rats, nilvadipine significantly increases the expression of rhodopsin kinase and alphaA-crystallin while suppressing the expression of caspase 1 and 2.[3] In rat aortae and human middle cerebral arteries, nilvadipine totally suppresses the vasoactivity that Abeta induces. Without significantly altering the CBF of control mice, nilvadipine raises cortical perfusion levels in Tg APPsw to levels comparable to those seen in control littermates.[4] Nilvadipine suppresses mice's ischemia (20 min)-reflow (20 min)-induced paw edema (ED30: 0.4 mg/kg i.v. and 2 mg/kg p.o.). Nilvadipine suppresses paw edema caused by carrageenan (ED30:15 mg/kg in rats and 20 mg/kg in mice) with a potency comparable to ibuprofen, an anti-inflammatory medication. In rats, oral dosages of 100 mg/kg of nifedipine, nicardipine, and nimodipine cause a 30% suppression. Using the lactate dehydrogenase + NADH method and the cytochrome c method, nilvadipine inhibits the production of superoxide radical (O-2), as measured by IC50 values of 90 and 100 mg/mL, respectively, from xanthine oxidase (XOD).[5]
Animal Protocol	In the present study, 3- to 5-week-old inbred RCS (rdy-/-) rats reared in cyclic light conditions (12 hours on-12 hours off) are used. Nilvadipine and Nifedipine are dissolved in a mixture of ethanol, polyethylene glycol 400, and distilled water (2:1:7) at a concentration of 0.1 mg/mL, diluted twice with physiological saline before use, and injected intraperitoneally (1.0 mL/kg) into anesthetized rats every day early in the morning for 2 weeks. In control rats, the same solution without Nilvadipine or Nifedipine (vehicle solution) is administered similarly. Nicardipine and Diltiazem are dissolved in PBS at 0.25 mg/mL and 1 mg/mL, respectively, and injected intraperitoneally (1 mL/kg), similarly to the other agonists. As a control, the same volume of a mixture of ethanol, polyethylene glycol 400, and distilled water (2:1:7) or PBS is administered. Before administration, the pH of all drug solutions is adjusted to approximately 7.4. The concentrations of these drugs administered to RCS rats are determined by their concentrations in oral administration to human patients with hypertension for 1 day in our clinical practice (Nilvadipine, 0.05-0.3 mg/kg; Nifedipine, 0.1-0.5 mg/kg; Nicardipine, 0.2-1 mg/kg; and Diltiazem, 0.3-3 mg/kg). Rats
References	[1]. Atherosclerosis . 1988 Aug;72(2-3):213-9. [2]. J Cardiovasc Pharmacol . 1999 Feb;33(2):243-7. [3]. Invest Ophthalmol Vis Sci . 2002 Apr;43(4):919-26. [4]. Brain Res . 2004 Feb 27;999(1):53-61. [5]. Arzneimittelforschung . 1991 May;41(5):469-74.
Additional Infomation	Nilvadipine is an isopropyl ester, a methyl ester, a nitrile and a dihydropyridine. Nilvadipine is a calcium channel blocker (CCB) for the treatment of hypertension. Drug Indication For the management of vasospastic angina, chronic stable angina and hypertension. Mechanism of Action Nilvadipine inhibits the influx of extracellular calcium through myocardial and vascular membrane pores by physically plugging the channel. The decrease in intracellular calcium inhibits the contractile processes of 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.

Solubility Data

Solubility (In Vitro)

DMSO: ~77 mg/mL (~199.8 mM) Water: <1 mg/mL Ethanol: ~33 mg/mL (~85.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 3.33 mg/mL (8.64 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 33.3 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. Solubility in Formulation 2: 3.33 mg/mL (8.64 mM) 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; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 33.3 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. Solubility in Formulation 3: ≥ 3.33 mg/mL (8.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 33.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5949 mL	12.9745 mL	25.9491 mL
	5 mM	0.5190 mL	2.5949 mL	5.1898 mL
	10 mM	0.2595 mL	1.2975 mL	2.5949 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.