NITRENDIPINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C18H20N2O6
Molecular Weight	360.3612
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)C1=C(C)NC(C)=C(C1C2=CC(=CC=C2)[N+]([O-])=O)C(=O)OC

InChI

InChIKey=PVHUJELLJLJGLN-UHFFFAOYSA-N

InChI=1S/C18H20N2O6/c1-5-26-18(22)15-11(3)19-10(2)14(17(21)25-4)16(15)12-7-6-8-13(9-12)20(23)24/h6-9,16,19H,5H2,1-4H3

HIDE SMILES / InChI

Molecular Formula	C18H20N2O6
Molecular Weight	360.3612
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.hmdb.ca/metabolites/HMDB15187
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/68009568

Nitrendipine is a calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive. By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, nitrendipine 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Intermediate conductance calcium-activated potassium channel protein 4 8 Target ID: CHEMBL4305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10884437	Inhibitor 8146	0.9 µM [Kd]
Voltage-gated L-type calcium channel alpha-1C subunit 44 Target ID: CHEMBL2529 Sources: https://www.drugbank.ca/drugs/DB01054	Blocker 530	0.97 nM [IC50]
Voltage-gated L-type calcium channel alpha-1C subunit 44 Target ID: CHEMBL2830 Sources: https://www.drugbank.ca/drugs/DB01054	Blocker 530	1.08 nM [IC50]
Voltage-gated L-type calcium channel alpha-1D subunit 2 Target ID: CHEMBL4138 Sources: https://www.drugbank.ca/drugs/DB01054	Blocker 530	3.59 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 546 Sources: http://www.webhealthcentre.com/drugix/Nitrendipine_DI0096.aspx	Primary		Approved 8307	Nitrendipine Approved Use Nitrendipine is used to treat mild to moderate hypertension.

PubMed

Title	Date	PubMed
Systemic and regional hemodynamics in normotensive and spontaneously hypertensive rats after slow-channel calcium blocker nitrendipine.	1984	6733943
Mode of antihypertensive action of nitrendipine.	1984	6085384
The protective effect of nitrendipine on gentamicin acute renal failure in rats.	1985 Aug	3159593
Predictors of blood pressure increases after withdrawal of antihypertensive therapy.	1985 Dec	2856766
Relative potency of a beta-blocking and a calcium entry blocking agent as antihypertensive drugs in black patients.	1986	2869952
Renal effects of 1,4-dihydropyridines in animal models of hypertension and renal failure.	1987	2441191
Nitrendipine-stimulated release of prostacyclin-like substance in normal and atherosclerotic animals.	1987 Apr	3300663
Effects of nitrendipine and cilazapril alone or in combination on hemodynamics and regional blood flows in conscious spontaneously hypertensive rats.	1988	2468061
Calcium currents in embryonic and neonatal mammalian skeletal muscle.	1988 Jun	2458429
Cosecretion of calcitonin and calcitonin gene-related peptide from cultured rat medullary thyroid C cells.	1989 Feb	2470235
Nitrendipine versus hydrochlorothiazide in hypertensive patients over 70 years of age.	1989 Mar	2920503
[The effect of calcium antagonist nitrendipine on the morphological picture of experimentally-produced myocardial injuries in rats].	1990	2327189
Effects of nitrendipine and atenolol on blood pressure and intracellular sodium in hypertensive blacks.	1990 Apr	2338698
Systemic and regional hemodynamic interactions of perindopril and nitrendipine in the spontaneously hypertensive rat.	1990 Apr	1691399
Lacidipine: a calcium antagonist with potent and long-lasting antihypertensive effects in animal studies.	1990 Apr	1691398
Preclinical pharmacology of Ro 31-6930, a new potassium channel opener.	1990 Feb	1689412
Nitrendipine decreases benzodiazepine withdrawal seizures but not the development of benzodiazepine tolerance or withdrawal signs.	1990 Nov	1963805
Regression of cardiovascular structural changes after long-term antihypertensive treatment with the calcium antagonist nitrendipine.	1991	1725798
Tolerance to nitrendipine in patients with arterial hypertension accompanying chronic renal failure.	1991	1723462
Microvascular effects of cocaine; interaction with nitrendipine and enalaprilat.	1991	1646895
The place of isradipine in the treatment of hypertension.	1991 Feb	1827026
Acute and short-term effects of nitrendipine and diltiazem at rest and during exercise in hypertensive patients.	1991 Nov-Dec	1790542
Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension.	1992 Aug	1639466
Arterial and antihypertensive effects of nitrendipine: a double-blind comparison versus placebo.	1992 Dec	1282585
Effects of nitrendipine, chlordiazepoxide, flumazenil and baclofen on the increased anxiety resulting from alcohol withdrawal.	1992 Jan	1557510
Nocturnal hypotension and ACE inhibitors.	1993 Jun	8345498
Treatment of hypertensive emergency. Comparison of a new dosage form of the calcium antagonist nitrendipine with nifedipine capsules.	1994	8046120
Combination treatment of enalapril with nitrendipine in rats with renovascular hypertension.	1994 Jan	8282322
Delayed development of hypertension after short-term nitrendipine treatment.	1994 Jul	8021001
Doxazosin versus nitrendipine: a double-blind comparative study in patients adhering to a sodium-restricted diet.	1994 Jun	7947364
Effect of indomethacin on blood pressure control during treatment with nitrendipine.	1995 Sep	8535553
Influence of the angiotensin II type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals.	1996 Dec	8952600
Antihypertensive effects of trandolapril and nitrendipine in the elderly: a controlled trial with special emphasis on time effect profiles.	1996 Jan	8642191
Nitrendipine and enalapril improve albuminuria and glomerular filtration rate in non-insulin dependent diabetes.	1996 Jun	8743521
L-type calcium channels regulate gastrin release from human antral G cells.	1997 Aug	9277405
Evaluation of the efficacy and tolerability of nitrendipine in reducing both pressure and left ventricular mass in hypertensive type 2 diabetic patients.	1997 Aug	9250456
Characterization of the cloned human intermediate-conductance Ca2+-activated K+ channel.	1998 Sep	9730970
Haloperidol-induced catalepsy is influenced by calcium channel antagonists.	2000 May-Jun	11143713
Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines.	2001 Aug 15	11487617
Nitrendipine-induced subacute cutaneous lupus erythematosus.	2003 Mar-Apr	12695145
Enhanced interleukin-4 production in CD4+ T cells and elevated immunoglobulin E levels in antigen-primed mice by bisphenol A and nonylphenol, endocrine disruptors: involvement of nuclear factor-AT and Ca2+.	2003 May	12709020
[Effects of nitrendipine on circadian variation of blood pressure in inpatients with renal parenchymal hypertension: assessment by ambulatory blood pressure monitoring].	2004 Jul	15446599
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.	2004 Nov	15286053
Synergism of hydrochlorothiazide and nitrendipine on reduction of blood pressure and blood pressure variability in spontaneously hypertensive rats.	2006 Dec	17112411
Differential roles of dihydropyridine calcium antagonist nifedipine, nitrendipine and amlodipine on gentamicin-induced renal tubular toxicity in rats.	2009 Oct 12	19698708
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.	2010 Dec	20829430
Prevention of hypertensive crises in rats induced by acute and chronic norepinephrine excess.	2010 Oct	20665428
Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11).	2013 Dec	24014644
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.	2013 Sep 5	23769903
Deoxynivalenol (Vomitoxin)-Induced Cholecystokinin and Glucagon-Like Peptide-1 Release in the STC-1 Enteroendocrine Cell Model Is Mediated by Calcium-Sensing Receptor and Transient Receptor Potential Ankyrin-1 Channel.	2015 Jun	25787141

Patents

Sample Use Guides

In Vivo Use Guide

Start with 5-20 mg once daily. May be increased to 40 mg in 1 or 2 doses. In hepatic disease reduce the dose to 5 to 10 mg daily.

Route of Administration: Oral

In Vitro Use Guide

At 1 and 10 uM, nitrendipine reduced peak Cav1.2a1 currents by 64+/-3% (n=4) and 81+/-1% (n=4), respectively, but at these same concentrations only inhibited Cav1.3a1 currents by 23+/-1% (n=8) and 53+/-2% (n=8), respectively.

Substance Class	Chemical Created by `admin` on `Sun Dec 18 19:23:39 UTC 2022` Edited by `admin` on `Sun Dec 18 19:23:39 UTC 2022`
Record UNII	9B627AW319
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

NITRENDIPINE

Official Name

English

3,5-PYRIDINEDICARBOXYLIC ACID, 1,4-DIHYDRO-2,6-DIMETHYL-4-(3-NITROPHENYL)-, ETHYL METHYL ESTER

Common Name

English

NITRENDIPINE [USAN]

Common Name

English

NITRENDIPINE [EP MONOGRAPH]

Common Name

English

BAYPRESS

Brand Name

English

BAY-E-5009

Code

English

(±)-BAY-E-5009

Code

English

NSC-758466

Code

English

NITRENDIPINE [MI]

Common Name

English

NITRENDIPINE [MART.]

Common Name

English

(±)-ETHYL METHYL 1,4-DIHYDRO-2,6-DIMETHYL-4-(M-NITROPHENYL)-3,5-PYRIDINEDICARBOXYLATE

Systematic Name

English

NIDREL

Common Name

English

NITRENDIPINE [JAN]

Common Name

English

3,5-PYRIDINEDICARBOXYLIC ACID, 1,4-DIHYDRO-2,6-DIMETHYL-4-(3-NITROPHENYL)-, 3-ETHYL 5-METHYL ESTER

Common Name

English

NITREPIN

Common Name

English

(±)-NITRENDIPINE

Common Name

English

Nitrendipine [WHO-DD]

Common Name

English

DEITEN

Common Name

English

NITRENDIPINE [EP IMPURITY]

Common Name

English

BAYOTENSIN

Brand Name

English

3,5-PYRIDINEDICARBOXYLIC ACID, 1,4-DIHYDRO-2,6-DIMETHYL-4-(3-NITROPHENYL)-, ETHYL METHYL ESTER, (±)-

Common Name

English

nitrendipine [INN]

Common Name

English

BAY E 5009

Code

English

Classification Tree Code System Code

WHO-VATC

QC09BB06