Nisoldipine

Names

[ Name ]:
Nisoldipine

[Synonym ]:
methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, methyl 2-methylpropyl ester
EINECS 264-407-7
Nisoldipine
Isobutyl 1,4-Dihydro-5-methoxycarbonyl-2,6-dimethyl-4-(2-nitrophenyl)-3-pyridinecarboxylate
3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, methyl 2-methylpropyl ester
Isobutyl Methyl 1,4-Dihydro-2,6-dimethyl-4-(o-nitrophenyl)-3,5-pyridinedicarboxylate
MFCD00478055
3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Isobutyl methyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
2,6-Dimethyl-3-carbomethoxy-4-(2-nitrophenyl)-5-carbisobutoxy-1,4-dihydropyridine
Baymycard
Isobutyl methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate
UNII:4I8HAB65SZ
Syscor
1,4-Dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic Acid Methyl 2-Methylpropyl Ester
Zadipina
Isobutyl methyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate

Biological Activity

[Description]:

Nisoldipine(BAY-k 5552; Sular) is a calcium channel blocker belonging to the dihydropyridines class, specific for L-type Cav1.2 with IC50 of 10 nM. IC50 value: 10 nMTarget: L-type Cav1.2Nisoldipine is a potent blocker of L-type calcium channels. Nisoldipine binds directly to inactive calcium channels stabilizing their inactive conformation Similar to other DHP CCBs. Nisoldipine displays selectivity for arterial smooth muscle cells due to great number of inactive channels and the α1 subunit of the channel. Nisoldipine is about 30 times less selective for delayed-rectifier K+ channels than for L-type Ca2+ channels, which inhibits IKr (rapidly activating delayed-rectifier K+ current) with IC50 of 23 μM, and IKs (slowly activating delayed-rectifier K+ current)with IC50 of 40 μM in guinea-pig ventricular myocytes. Nisoldipine also displays antioxidant potency with IC50 of 28.2 μM both before and after the addition of active oxygen.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel

Research Areas >> Cardiovascular Disease

[References]

[1]. Hamilton SF, Houle LM, Thadani U. Rapid-release and coat-core formulations of nisoldipine in treatment of hypertension, angina, and heart failure. Heart Dis. 1999 Nov-Dec;1(5):279-88.

[2]. Fodor JG. Nisoldipine CC: efficacy and tolerability in hypertension and ischemic heart disease. Cardiovasc Drugs Ther. 1997 Jan;10 Suppl 3:873-9.

[3]. D.J. Duncker, J.M. Hartog, P.G. Hugenholtz, et al. The effects of nisoldipine (Bay K 5552) on cardiovascular performance and regional blood flow in pentobarbital - anaesthetized pigs with or without β-adrenoceptor blockade. British Journal of Pharmacology

[4]. Jan W. De Jong, Tom Huizer, Jan G.P. Tijssen. Energy conservation by nisoldipine in ischaemic heart. British Journal of Pharmacology. 1984, 83(4): 943-949

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
505.8±50.0 °C at 760 mmHg

[ Melting Point ]:
147-148°C

[ Molecular Formula ]:
C₂₀H₂₄N₂O₆

[ Molecular Weight ]:
388.414

[ Flash Point ]:
259.7±30.1 °C

[ Exact Mass ]:
388.163422

[ PSA ]:
110.45000

[ LogP ]:
4.38

[ Vapour Pressure ]:
0.0±1.3 mmHg at 25°C

[ Index of Refraction ]:
1.544

[ Storage condition ]:
-20°C Freezer

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: US7975600

CHEMICAL NAME :: 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, methyl 2-methyl propyl ester

CAS REGISTRY NUMBER :: 63675-72-9

LAST UPDATED :: 199612

DATA ITEMS CITED :: 10

MOLECULAR FORMULA :: C20-H24-N2-O6

MOLECULAR WEIGHT :: 388.46

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1257 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - cyanosis Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,3285,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 674 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Skin and Appendages - hair

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,3285,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1120 ug/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,3285,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 411 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - cyanosis Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,3285,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 384 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Skin and Appendages - hair

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,3285,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 360 ug/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes Skin and Appendages - hair

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 22,3285,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 400 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,682,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 2 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,243,1983

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,243,1983

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 2500 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,243,1983

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H312

[ Precautionary Statements ]:
P280

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
R36/37/38:Irritating to eyes, respiratory system and skin .

[ Safety Phrases ]:
S26-S36

[ RIDADR ]:
3077

[ WGK Germany ]:
2

[ RTECS ]:
3425000

[ HS Code ]:
2942000000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2942000000

Articles

Fast disintegrating tablets of nisoldipine for intra-oral administration.

Pharm. Dev. Technol. 19(6) , 641-50, (2014)

Nisoldipine is a calcium channel blocker with low and variable oral bioavailability. This was attributed to slow dissolution and presystemic metabolism. Accordingly, the objective of this work was to ...

Anti-arrhythmic and hemodynamic effects of oxy nifedipine, oxy nimodipine, oxy nitrendipine and oxy nisoldipine.

Pharmacol. Res. 66(4) , 300-8, (2012)

Our previous studies have established cardio-protective effects of furnidipine and its active metabolites. We therefore decided to compare the influence of oral and intravenous administration of furni...

Why is nisoldipine a specific agent in ischemic left ventricular dysfunction?

Am. J. Cardiol. 75(13) , 36E-40E, (1995)

Nisoldipine is a dihydropyridine calcium entry blocker that inhibits contraction of vascular smooth muscle with a potency that is 2-3 times greater than its impact on myocardial contractility. In isol...