AZELNIDIPINE

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C33H34N4O6
Molecular Weight	582.6463
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)OC(=O)C1=C(C)NC(N)=C(C1C2=CC=CC(=C2)[N+]([O-])=O)C(=O)OC3CN(C3)C(C4=CC=CC=C4)C5=CC=CC=C5

InChI

InChIKey=ZKFQEACEUNWPMT-UHFFFAOYSA-N

InChI=1S/C33H34N4O6/c1-20(2)42-32(38)27-21(3)35-31(34)29(28(27)24-15-10-16-25(17-24)37(40)41)33(39)43-26-18-36(19-26)30(22-11-6-4-7-12-22)23-13-8-5-9-14-23/h4-17,20,26,28,30,35H,18-19,34H2,1-3H3

HIDE SMILES / InChI

Molecular Formula	C33H34N4O6
Molecular Weight	582.6463
Charge	0
Count

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

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/14636080
Curator's Comment: description was created based on several sources, including http://www.ube-ind.co.jp/english/news/2003/2003_03.htm

Azelnidipine (INN; marketed under the brand name CalBlock) is a dihydropyridine calcium channel blocker. It is sold in Japan by Daiichi-Sankyo pharmaceuticals, Inc. Azelnidipine is a new dihydropyridine calcium channel antagonist with selectivity for both L-type and T-type Ca channels. It has recently been approved in Japan for the treatment of patients with hypertension. Results from clinical trials showed that long-term treatment with azelnidipine effectively controls blood pressure (BP) in a cohort of 95 patients with mild-to-moderate hypertension. The antihypertensive efficacy of azelnidipine in patients with mild-to-moderate hypertension was shown to be similar to that of amlodipine or nitrendipine in a randomised double-blind study. Azelnidipine and amlodipine controlled 24-hour BP to a similar extent. Azelnidipine is generally well tolerated. Vasodilator adverse events such as headache and hot facial flushes account for most of the adverse events. Its use is not associated with reflex tachycardia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated L-type calcium channel 95 Target ID: CHEMBL2095229 Sources: http://www.ncbi.nlm.nih.gov/pubmed/20881449	Blocker 555
Voltage-gated T-type calcium channel 19 Target ID: CHEMBL2362995 Sources: http://www.ncbi.nlm.nih.gov/pubmed/20881449	Blocker 555

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: http://www.ube-ind.co.jp/english/rd/pharmaceuticals_calblock.htm	Primary		Approved 8583	Calblock Approved Use Unknown Launch Date 2003

C_max

Value	Dose	Analyte	Population
48.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12675275/	16 mg 1 times / day steady-state, oral dose: 16 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
5.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16920318/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
8.66 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18771003/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
19.17 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18771003/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
15.04 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18771003/	8 mg 1 times / day steady-state, oral dose: 8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
426 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12675275/	16 mg 1 times / day steady-state, oral dose: 16 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
53.6 ng × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16920318/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
186 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18771003/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
429 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18771003/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
169.19 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18771003/	8 mg 1 times / day steady-state, oral dose: 8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
8.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12675275/	16 mg 1 times / day steady-state, oral dose: 16 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16920318/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
22.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18771003/	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
23.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18771003/	16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered:	AZELNIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% REVIEW https://pubmed.ncbi.nlm.nih.gov/14636080/	single, unknown		AZELNIDIPINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
24 mg 1 times / day multiple, oral Highest studied dose Dose: 24 mg, 1 times / day Route: oral Route: multiple Dose: 24 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/	Other AEs: Dizziness, Dizziness postural... Other AEs: Dizziness (0.42%) Dizziness postural (0.04%) Headache (0.32%) Hot flushes (0.17%) Palpitations (0.11%) Edema (0.04%) Edema peripheral (0.09%) Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/
16 mg 1 times / day multiple, oral Recommended Dose: 16 mg, 1 times / day Route: oral Route: multiple Dose: 16 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21029001/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/21029001/	Sources: https://pubmed.ncbi.nlm.nih.gov/21029001/

AEs

AE	Significance	Dose	Population
Dizziness postural	0.04%	24 mg 1 times / day multiple, oral Highest studied dose Dose: 24 mg, 1 times / day Route: oral Route: multiple Dose: 24 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/
Edema	0.04%	24 mg 1 times / day multiple, oral Highest studied dose Dose: 24 mg, 1 times / day Route: oral Route: multiple Dose: 24 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/
Edema peripheral	0.09%	24 mg 1 times / day multiple, oral Highest studied dose Dose: 24 mg, 1 times / day Route: oral Route: multiple Dose: 24 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/
Palpitations	0.11%	24 mg 1 times / day multiple, oral Highest studied dose Dose: 24 mg, 1 times / day Route: oral Route: multiple Dose: 24 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/
Hot flushes	0.17%	24 mg 1 times / day multiple, oral Highest studied dose Dose: 24 mg, 1 times / day Route: oral Route: multiple Dose: 24 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/
Headache	0.32%	24 mg 1 times / day multiple, oral Highest studied dose Dose: 24 mg, 1 times / day Route: oral Route: multiple Dose: 24 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/
Dizziness	0.42%	24 mg 1 times / day multiple, oral Highest studied dose Dose: 24 mg, 1 times / day Route: oral Route: multiple Dose: 24 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/23512719/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087 inhibitor 2252	substrate 1193 inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 926 CYP19A1 429 CYP2J2 33 CYP3A5 136 CYP2A6 879 CYP2C19 2057 CYP1A2 2153 CYP2E1 1060	CYP1A1 389 CYP2B6 776 CYP2C8 810 P-gp 2052 CYP2A6 626 CYP1A2 1197 CYP2E1 729 CYP2C19 1119 CYP4A11 137

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W105_2.pdf#page=4 Page: 4.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W105_2.pdf#page=4 Page: 4.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W105_2.pdf#page=4 Page: 4.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/65948#section=Biological-Test-Results Page: 87.0	no
CYP2J2 36	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/30965050/	yes [IC50 0.137 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/65948#section=Biological-Test-Results Page: 33.0	yes [IC50 29.8493 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W105_2.pdf#page=4 Page: 4.0	yes [IC50 <50 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W105_2.pdf#page=4 Page: 4.0	yes [IC50 <50 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W105_2.pdf#page=4 Page: 4.0	yes [IC50 <50 uM]
CYP3A5 201	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W105_2.pdf#page=4 Page: 4.0	yes [IC50 <50 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24379677/	yes [Ki 0.0181 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W105_2.pdf#page=4 Page: 4.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/65948#section=BioAssay-Results Page: 19 \| 87	inconclusive
CYP1A1 389	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W104_2.pdf#page=10 Page: 10.0	likely
CYP1A2 1197	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W104_2.pdf#page=10 Page: 10.0	likely
CYP2A6 626	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W104_2.pdf#page=10 Page: 10.0	likely
CYP2B6 776	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W104_2.pdf#page=10 Page: 10.0	likely
CYP2C8 810	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W104_2.pdf#page=10 Page: 10.0	likely
CYP2C9 1193	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W104_2.pdf#page=10 Page: 10.0	likely
CYP2D6 1388	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W104_2.pdf#page=10 Page: 10.0	likely
CYP2E1 729	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W104_2.pdf#page=10 Page: 10.0	likely
CYP4A11 137	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W104_2.pdf#page=10 Page: 10.0	likely
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24379677/ \| https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_Q100_2.pdf#page=26 \| https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W106_2.pdf#page=8	major	yes (co-administration study) Comment: Itraconazole increased Azelnidipine Cmax by 1.75-fold, AUC0-tz by 2.80-fold, and AUCinf by 2.82-fold. Sources: https://pubmed.ncbi.nlm.nih.gov/24379677/ \| https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_Q100_2.pdf#page=26 \| https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W106_2.pdf#page=8
CYP2C19 1119	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2003/P200300002/30015600_21500AMZ00030_W104_2.pdf#page=10 Page: 10.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 63	supressor 11 Sources: https://pubmed.ncbi.nlm.nih.gov/33453240/
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/65948#section=BioAssay-Results Page: 15.0

PubMed

Title	Date	PubMed
Chronotropic effects of azelnidipine, a slow- and long-acting dihydropyridine-type calcium channel blocker, in anesthetized dogs: a comparison with amlodipine.	2009-04	19295444
Antihypertensive effects of CS-905, a novel dihydropyridine Ca++ channel blocker.	1989-09	2810942

Patents

Sample Use Guides

In Vivo Use Guide

The normal dose for an adult is 8-16 mg of azelnidipine once daily, taken orally after breakfast. The maximum dosage is 16 mg/day. The initial dosage is to be 8 mg/day or less, to be adjusted as symptoms are monitored, up to 16 mg daily.

Route of Administration: Oral

In Vitro Use Guide

azelnidipine inhibited rat aortic smooth muscle cell (RASMC) death in a concentration-dependent manner (10-100 nM) as well as inhibited JNK and p38 activation by mechanical stretch

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:23:35 GMT 2025` Edited by `admin` on `Mon Mar 31 18:23:35 GMT 2025`
Record UNII	PV23P19YUG
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CALBLOCK

Preferred Name

English

AZELNIDIPINE

Official Name

English

CS905

Code

English

AZELNIDIPINE [MI]

Common Name

English

CS-905

Code

English

azelnidipine [INN]

Common Name

English

AZELNIDIPINE [MART.]

Common Name

English

AZELNIDIPINE [JAN]

Common Name

English

3-(1-(DIPHENYLMETHYL)-3-AZETIDINYL) 5-ISOPROPYL (±)-2-AMINO-1,4-DIHYDRO-6-METHYL-4-(M-NITROPHENYL)-3,5-PYRIDINEDICARBOXYLATE

Systematic Name

English

Azelnidipine [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C333