Nisoldipine

Modify Date: 2024-01-02 22:24:55

Nisoldipine Structure
Nisoldipine structure
Common Name Nisoldipine
CAS Number 63675-72-9 Molecular Weight 388.414
Density 1.2±0.1 g/cm3 Boiling Point 505.8±50.0 °C at 760 mmHg
Molecular Formula C20H24N2O6 Melting Point 147-148°C
MSDS Chinese USA Flash Point 259.7±30.1 °C
Symbol GHS07
GHS07
Signal Word Warning

 Use of Nisoldipine


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.

 Names

Name methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Synonym More Synonyms

 Nisoldipine 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
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

 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

 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
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

~52%

Nisoldipine Structure

Nisoldipine

CAS#:63675-72-9

Literature: ERREGIERRE, S.P.A. Patent: WO2004/2958 A1, 2004 ; Location in patent: Page 4-5 ;

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Nisoldipine Structure

Nisoldipine

CAS#:63675-72-9

Literature: US5786344 A1, ;

 Customs

HS Code 2942000000

 Articles45

More 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...

 Synonyms

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
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