MANIDIPINE

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C35H38N4O6
Molecular Weight	610.6994
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC(=O)C1=C(C)NC(C)=C(C1C2=CC=CC(=C2)[N+]([O-])=O)C(=O)OCCN3CCN(CC3)C(C4=CC=CC=C4)C5=CC=CC=C5

InChI

InChIKey=ANEBWFXPVPTEET-UHFFFAOYSA-N

InChI=1S/C35H38N4O6/c1-24-30(34(40)44-3)32(28-15-10-16-29(23-28)39(42)43)31(25(2)36-24)35(41)45-22-21-37-17-19-38(20-18-37)33(26-11-6-4-7-12-26)27-13-8-5-9-14-27/h4-16,23,32-33,36H,17-22H2,1-3H3

HIDE SMILES / InChI

Molecular Formula	C35H38N4O6
Molecular Weight	610.6994
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/11693466
Curator's Comment: description was created based on several sources, including

Manidipine is a lipophilic, third-generation dihydropyridine calcium channel antagonist with a high degree of selectivity for the vasculature, thereby inducing marked peripheral vasodilation with negligible cardiodepression. In addition, manidipine does not significantly affect norepinephrine levels, suggesting a lack of sympathetic activation. It has a gradual onset of action and a long duration of action enabling once daily administration. Furthermore, manidipine dilates both the efferent and the afferent renal arterioles and appears to have beneficial renal effects unrelated to its antihypertensive effect. Once-daily oral manidipine is an effective and generally well tolerated antihypertensive agent for younger and elderly adult patients with mild-to-moderate hypertension. In particular, in a large double-blind trial, the incidence of ankle oedema was significantly lower in manidipine than in amlodipine recipients. Manidipine is also effective in hypertensive patients with comorbidities, such as type 2 diabetes mellitus and/or renal impairment, and appears to improve insulin sensitivity without affecting metabolic function. Thus, manidipinerepresents a first-line treatment option for patients with essential mild-to-moderate hypertension.

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/8287905	Antagonist 2849		400.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: http://www.ncbi.nlm.nih.gov/pubmed/11693466	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
3.15 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=28	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.94 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=29	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.1 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
11.6 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
15.1 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
9 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
12.2 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
8.6 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
6.5 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
11.7 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Analyte	Population
13.02 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=28	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
35.08 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=29	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
42.9 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
60.2 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
85.2 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
45.3 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
69.4 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
29.1 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
33.5 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
74.5 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Analyte	Population
4.92 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=28	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.31 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=29	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.25 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
8.3 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
11.2 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
8.9 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
15.5 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
3.9 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
4.8 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
8.4 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=31	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MANIDIPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.4% OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400813_2149027F1101_1_004_1F.pdf#page=32			MANIDIPINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
20 mg 1 times / day multiple, oral Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21155616/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21155616/	Sources: https://pubmed.ncbi.nlm.nih.gov/21155616/

PubMed

Title	Date	PubMed
Calcium channel blockades exhibit anti-inflammatory and antioxidative effects by augmentation of endothelial nitric oxide synthase and the inhibition of angiotensin converting enzyme in the N(G)-nitro-L-arginine methyl ester-induced hypertensive rat aorta: vasoprotective effects beyond the blood pressure-lowering effects of amlodipine and manidipine.	2005-08	16392774
Effect of successful hypertension control by manidipine or lisinopril on albuminuria and left ventricular mass in diabetic hypertensive patients with microalbuminuria.	2005-08	16021438
Manidipine versus enalapril monotherapy in patients with hypertension and type 2 diabetes mellitus: a multicenter, randomized, double-blind, 24-week study.	2005-02	15811479
Effect of manidipine on gene expression and protein level of oxidative stress-related proteins: p22phox and HO-1: relevance for antihypertensive and anti-remodeling effects.	2004-04	15085064
Interaction of digoxin with antihypertensive drugs via MDR1.	2002-02-15	11895100
Antihypertensive efficacy of manidipine and enalapril in hypertensive diabetic patients.	2000-06	10836728
Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions.	2000-05-11	10805063
Catalepsy induced by calcium channel blockers in mice.	1998-03	9533112
Effect of manidipine hydrochloride, a calcium antagonist, on isoproterenol-induced left ventricular hypertrophy.	1998-01	9559417
Role of angiotensin II in reflex tachycardia during hypotension caused by a calcium channel blocker.	1996-07	8781749
Regional vascular effects of MPC-1304, a novel dihydropyridine derivative, in conscious normotensive and spontaneously hypertensive rats.	1996-06	8667194
Catalepsy induced by manidipine, a calcium channel blocker, in mice.	1996-04	8794996

Patents

Sample Use Guides

In Vivo Use Guide

Manidipine 10 to 40 mg once daily for 4 weeks

Route of Administration: Oral

In Vitro Use Guide

Manidipine, at nanomolar concentrations, is efficacious in modulating gene transcriptions that are involved in proinflammatory changes of mesangial cells. Thus, manidipine, at pharmacological concentrations that are one to two orders of magnitude lower than those required for inhibition of agonist- or depolarization (K+)-induced vasoconstriction, causes changes in the activity of the genes that code for inflammatory mediators.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:40:13 GMT 2025` Edited by `admin` on `Mon Mar 31 18:40:13 GMT 2025`
Record UNII	6O4754US88
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MANIDIPINE

Official Name

English

ARTEDIL

Preferred Name

English

FRANIDIPINE

Common Name

English

(±)-MANIDIPINE

Common Name

English

MANIDIPINE [MI]

Common Name

English

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

Common Name

English

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

Common Name

English

MANIDIPINE 6300

Common Name

English

Manidipine [WHO-DD]

Common Name

English

manidipine [INN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC08CA11