NITRENDIPINE

Possibly Marketed Outside US

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

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

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Description

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 13	Inhibitor 8,504	0.9 µM [Kd]
Voltage-gated L-type calcium channel alpha-1C subunit 44	Blocker 555	0.97 nM [IC50]
Voltage-gated L-type calcium channel alpha-1C subunit 44	Blocker 555	1.08 nM [IC50]
Voltage-gated L-type calcium channel alpha-1D subunit 2	Blocker 555	3.59 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575	Primary		Approved 8,583	Nitrendipine

C_max

Value	Dose	Analyte	Population
8 ng/mL	20 mg single, oral	NITRENDIPINE plasma	Homo sapiens
3.31 ng/mL	40 mg single, oral	NITRENDIPINE plasma	Homo sapiens
18.1 ng/mL	2 mg single, intravenous	NITRENDIPINE serum	Homo sapiens
12.5 ng/mL	20 mg single, oral	NITRENDIPINE serum	Homo sapiens

AUC

Value	Dose	Analyte	Population
33.7 ng × h/mL	40 μg/kg bw single, intravenous	NITRENDIPINE plasma	Homo sapiens
5.56 ng × h/mL	40 μg/kg bw single, intravenous	DEHYDRONITRENDIPINE plasma	Homo sapiens
45.8 ng × h/mL	20 mg single, oral	DEHYDRONITRENDIPINE plasma	Homo sapiens
26.3 ng × h/mL	20 mg single, oral	NITRENDIPINE plasma	Homo sapiens
38.1 ng × h/mL	40 mg single, oral	NITRENDIPINE plasma	Homo sapiens
71.8 ng × h/mL	40 mg single, oral	DEHYDRONITRENDIPINE plasma	Homo sapiens
48.9 ng × h/mL	10 mg single, oral	NITRENDIPINE plasma	Homo sapiens
54.3 ng × h/mL	10 mg 1 times / day multiple, oral	NITRENDIPINE plasma	Homo sapiens
29.6 ng × h/mL	2 mg single, intravenous	NITRENDIPINE serum	Homo sapiens
65.2 ng × h/mL	20 mg single, oral	NITRENDIPINE serum	Homo sapiens
27.7 ng × h/mL	2 mg single, intravenous	NITRENDIPINE plasma	Homo sapiens
61.23 ng × h/mL	20 mg single, oral	NITRENDIPINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
11.7 h	40 μg/kg bw single, intravenous	NITRENDIPINE plasma	Homo sapiens
13.4 h	40 μg/kg bw single, intravenous	DEHYDRONITRENDIPINE plasma	Homo sapiens
11.5 h	20 mg single, oral	DEHYDRONITRENDIPINE plasma	Homo sapiens
12.7 h	20 mg single, oral	NITRENDIPINE plasma	Homo sapiens
13.6 h	40 mg single, oral	NITRENDIPINE plasma	Homo sapiens
14 h	40 mg single, oral	DEHYDRONITRENDIPINE plasma	Homo sapiens
3.6 h	10 mg single, oral	NITRENDIPINE plasma	Homo sapiens
3.43 h	10 mg 1 times / day multiple, oral	NITRENDIPINE plasma	Homo sapiens
10.4 h	2 mg single, intravenous	NITRENDIPINE serum	Homo sapiens
10.5 h	20 mg single, oral	NITRENDIPINE serum	Homo sapiens
8.56 h	2 mg single, intravenous	NITRENDIPINE plasma	Homo sapiens
7.85 h	20 mg single, oral	NITRENDIPINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.7%	2 mg single, intravenous		NITRENDIPINE serum	Homo sapiens
2%	2 mg single, intravenous		NITRENDIPINE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
60 mg 1 times / day multiple, oral Higher than recommended	unhealthy, ADULT
20 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT	Other AEs: Dizziness, Angina pectori...
40 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT	Disc. AE: Flushing, Palpitations...

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AEs

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AE	Significance	Dose	Population
Dizziness	grade 3, 1.2%	20 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT
Angina pectori	grade 3, 2.4%	20 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT
Flushing	Disc. AE	40 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT
Oedema	Disc. AE	40 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT
Palpitations	Disc. AE	40 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2,252 substrate 1,946	inhibitor 2,438	inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 879 OATP1B3 961 MRP4 290 CYP1A2 2,153 BSEP 550 CYP2E1 1,060 CYP2C19 2,057 MRP3 246 P-gp 1,741 CYP19A1 429 OATP1B1 1,079	P-gp 2,052

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 2,333	inhibitor 4,027	no [IC50 >10 uM]
CYP2A6 911	inhibitor 4,027	no [IC50 >10 uM]
CYP2D6 2,546	inhibitor 4,027	no [IC50 >10 uM]
CYP2E1 1,146	inhibitor 4,027	no [IC50 >10 uM]
CYP3A4 2,633	inhibitor 4,027	no [IC50 >10 uM]

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2,052	substrate 4,014	inconclusive
CYP3A4 1,946	substrate 4,014	yes		yes (co-administration study)

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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PubMed

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Title	Date	PubMed
Systemic and regional hemodynamics in normotensive and spontaneously hypertensive rats after slow-channel calcium blocker nitrendipine.	1984	6733943
Clinical and systemic hemodynamic effects of nitrendipine.	1984 Jun	6734029
Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state.	1984 Oct	6093100
Renal effects of 1,4-dihydropyridines in animal models of hypertension and renal failure.	1987	2441191
Cosecretion of calcitonin and calcitonin gene-related peptide from cultured rat medullary thyroid C cells.	1989 Feb	2470235

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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.

Show entries

Name

Type

Language

NITRENDIPINE

Official Name

English

BAYOTENSIN

Preferred 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

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Classification Tree

Code System

Code

ACE inhibitors and calcium channel blockers

WHO-VATC

QC09BB06

Dihydropyridine derivatives

WHO-ATC

C08CA08

Cation Channel Blocker

NCI_THESAURUS

C333

ACE inhibitors and calcium channel blockers

WHO-ATC

C09BB06

Dihydropyridine derivatives

WHO-VATC

QC08CA08

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Code System

Code

Type

Description

LACTMED

Nitrendipine

PRIMARY

DRUG BANK

DB01054

PRIMARY

ChEMBL

CHEMBL475534

PRIMARY

CHEBI

7582

PRIMARY

PUBCHEM

4507

PRIMARY

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ACTIVE MOIETY


					9B627AW319

NITRENDIPINE

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator