NILVADIPINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H19N3O6
Molecular Weight	385.3707
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=FAIIFDPAEUKBEP-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C19H19N3O6
Molecular Weight	385.3707
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/HMDB15657
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/7898101

Nilvadipine (NIVADIL®) is a L-type calcium channel blocker for treatment of hypertension. It 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated L-type calcium channel alpha-1C subunit 44 Target ID: CHEMBL2830 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7898101	Blocker 555

Conditions

Condition	Modality	Targets	Highest Phase	Product
Essential hypertension 17 Sources: http://www.medicines.ie/medicine/3202/SPC#INDICATIONS	Primary		Approved 8583	NIVADIL Approved Use Nivadil is indicated for the treatment of essential hypertension. Launch Date 1996
Alzheimer’s disease 278 Sources: http://www.archerpharma.com/products&research.html	Primary		Phase III 665	Nilvadipine Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1.48 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680562/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.48 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680562/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.69 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680562/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.51 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3392233/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3.22 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3392233/	4 mg 2 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3.21 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3392233/	4 mg 2 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
5.67 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680587/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680587/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.33 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680587/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: LOW-FAT
4.61 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680587/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT

AUC

Value	Dose	Analyte	Population
5.28 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680562/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680562/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
18.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680562/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3392233/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
11.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3392233/	4 mg 2 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
12.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3392233/	4 mg 2 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
16.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680587/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680587/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
17.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680587/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: LOW-FAT
15.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680587/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT

T_1/2

Value	Dose	Analyte	Population
10.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680562/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680562/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3680562/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3392233/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
14.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3392233/	4 mg 2 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NILVADIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.3% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3563108/			NILVADIPINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/	Disc. AE: Lower limbs oedema... Other AEs: Lower limbs oedema, Headache... AEs leading to discontinuation/dose reduction: Lower limbs oedema Other AEs: Lower limbs oedema (20.0%) Headache (26.0%) Flushing (18.0%) Dizziness (6.0%) Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21905098/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21905098/	Sources: https://pubmed.ncbi.nlm.nih.gov/21905098/

AEs

AE	Significance	Dose	Population
Flushing	18.0%	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/
Lower limbs oedema	20.0%	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/
Headache	26.0%	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/
Dizziness	6.0%	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/
Lower limbs oedema	Disc. AE	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15969895/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 429 BSEP 550 P-gp 1741 CYP2B6 926 CYP2E1 1060 CYP1A2 2153 CYP2A6 879 CYP2C8/9 42 CYP2C19 2057	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/14993813/	no [Ki >40 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/14993813/	no [Ki >40 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/14993813/	no [Ki >40 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4494#section=Biological-Test-Results Page: 1.0	yes [IC50 0.5012 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4494#section=Biological-Test-Results Page: 2.0	yes [IC50 1.0684 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDUxNzQyNyJ9fQ==	yes [IC50 18 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4494#section=Biological-Test-Results Page: 9.0	yes [IC50 29.8493 uM]
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDUxNzQyNyJ9fQ==	yes [IC50 <10 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/14993813/	yes [Ki 13 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/14993813/	yes [Ki 24.5 uM]
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/14993813/	yes [Ki 35.8 uM]
CYP2C8/9 42	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/14993813/	yes [Ki 5.02 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4494#section=Biological-Test-Results Page: 6 \| 53	inconclusive

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4494#section=Biological-Test-Results Page: 31.0

PubMed

Title	Date	PubMed
Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats.	2004-04	15127885
Angiotensin II regulation of vascular endothelial growth factor and receptors Flt-1 and KDR/Flk-1 in cyclosporine nephrotoxicity.	2002-08	12110003
Interaction of digoxin with antihypertensive drugs via MDR1.	2002-02-15	11895100
Effects of nilvadipine (a dihydropyridine-type calcium entry blocker) on cerebral blood flow in acute experimental brain ischemia in rats.	1996-08	8875450
Tacrolimus (FK506)-induced nephrotoxicity in spontaneous hypertensive rats.	1994-11	7533848

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is 1 NIVADIL® 8 mg prolonged release capsule per day in the morning as a starting dose. If after 2 - 4 weeks of therapy an adequate anti-hypertensive effect is not achieved, a daily dose of 16 mg nilvadipine (2 x 8 mg NIVADIL® prolonged release capsules, or 1 x 16 mg NIVADIL® prolonged release capsule, in the morning) may improve the blood pressure response.

Route of Administration: Oral

In Vitro Use Guide

The cardiovascular effect of nilvadipine (FR34235) with the effects of nifedipine, nicardipine, and diltiazem on the dog using in vitro arterial strip preparations was compared. FR34235 reduced the amplitude of coronary arterial contraction induced by K+ more so than that induced by norepinephrine in in vitro preparations. The ID50 values of FR34235 for various arterial strips contracted by K+ were smaller (1/5-1/426) than those of nifedipine and diltiazem, and almost the same as those of nicardipine.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:52:36 GMT 2025` Edited by `admin` on `Mon Mar 31 17:52:36 GMT 2025`
Record UNII	0214FUT37J
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NIVADIL

Preferred Name

English

NILVADIPINE

Official Name

English

FK 235

Code

English

NILVADIPINE [JAN]

Common Name

English

NIVADIPINE

Common Name

English

NILVADIPINE [MART.]

Common Name

English

NILVADIPINE [USAN]

Common Name

English

nilvadipine [INN]

Common Name

English

CL-287,389

Code

English

SK&F-102362

Code

English

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

Common Name

English

ESCOR

Brand Name

English

5-ISOPROPYL 3-METHYL 2-CYANO-1,4-DIHYDRO-6-METHYL-4-(M-NITROPHENYL)-3,5-PYRIDINEDICARBOXYLATE

Systematic Name

English

CL 287,389

Code

English

CL-287389

Code

English

SK&F-102,362

Code

English

(±)-NILVADIPINE

Common Name

English

NIVADIP

Brand Name

English

FK-235

Code

English

NILVADIPINE [MI]

Common Name

English

Nilvadipine [WHO-DD]

Common Name

English

DL-NILVADIPINE

Common Name

English

SKF-102362

Code

English

FR-34235

Code

English

SK&F 102,362

Code

English

Classification Tree Code System Code

WHO-ATC

C08CA10