CILNIDIPINE

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C27H28N2O7
Molecular Weight	492.5204
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

COCCOC(=O)C1=C(C)NC(C)=C(C1C2=CC(=CC=C2)[N+]([O-])=O)C(=O)OC\C=C\C3=CC=CC=C3

InChI

InChIKey=KJEBULYHNRNJTE-DHZHZOJOSA-N

InChI=1S/C27H28N2O7/c1-18-23(26(30)35-14-8-11-20-9-5-4-6-10-20)25(21-12-7-13-22(17-21)29(32)33)24(19(2)28-18)27(31)36-16-15-34-3/h4-13,17,25,28H,14-16H2,1-3H3/b11-8+

HIDE SMILES / InChI

Molecular Formula	C27H28N2O7
Molecular Weight	492.5204
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

Cilnidipine (FRC-8653) is a dihydropyridine (DHP) type of calcium channel antagonist. The L-type Ca2+ channel blockade by cilnidipine affects predominantly vascular smooth muscle, thereby producing vasodilation of peripheral resistance vessels and coronary arteries. The blockade of N-type Ca2+ channels affects predominantly peripheral nerve endings of sympathetic neurons, thereby dilating blood vessels by lowering plasma catecholamine levels. Furthermore, renoprotective and neuroprotective effects as well as cardioprotective action of cilnidipine have been demonstrated in clinical practice or animal examinations. Cilnidipine was originated by Fuji & Rebio Pharmaceutical Co., Ltd. and developed jointly with Ajinomoto for the treatment of hypertension. Cilnidipine has been launched in Japan.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated L-type calcium channel	Inhibitor		4.77 null [pIC50]
Voltage-gated N-type calcium channel alpha-1B subunit	Inhibitor		6.08 null [pIC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypertension	Primary	Approved	ATELEC
Stroke	Primary	Preclinical	Unknown
Pain	Primary	Preclinical	Unknown

C_max

Value	Dose	Analyte	Population
4.7 ng/mL	5 mg single, oral	CILNIDIPINE plasma	Homo sapiens
5.4 ng/mL	10 mg single, oral	CILNIDIPINE plasma	Homo sapiens
15.7 ng/mL	20 mg single, oral	CILNIDIPINE plasma	Homo sapiens
9.5 ng/mL	10 mg 1 times / day multiple, oral	CILNIDIPINE plasma	Homo sapiens
13.5 ng/mL	10 mg 1 times / day multiple, oral	CILNIDIPINE plasma	Homo sapiens
16.5 ng/mL	10 mg 1 times / day steady-state, oral	CILNIDIPINE plasma	Homo sapiens
2.4 ng/mL	5 mg single, oral	CILNIDIPINE plasma	Homo sapiens
8.6 ng/mL	10 mg single, oral	CILNIDIPINE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
23.7 ng × h/mL	5 mg single, oral	CILNIDIPINE plasma	Homo sapiens
27.5 ng × h/mL	10 mg single, oral	CILNIDIPINE plasma	Homo sapiens
60.1 ng × h/mL	20 mg single, oral	CILNIDIPINE plasma	Homo sapiens
51.4 ng × h/mL	10 mg 1 times / day multiple, oral	CILNIDIPINE plasma	Homo sapiens
101.8 ng × h/mL	10 mg 1 times / day multiple, oral	CILNIDIPINE plasma	Homo sapiens
95.5 ng × h/mL	10 mg 1 times / day steady-state, oral	CILNIDIPINE plasma	Homo sapiens
11.6 ng × h/mL	5 mg single, oral	CILNIDIPINE plasma	Homo sapiens
46.1 ng × h/mL	10 mg single, oral	CILNIDIPINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
5.2 h	10 mg 1 times / day multiple, oral	CILNIDIPINE plasma	Homo sapiens
8.1 h	10 mg 1 times / day steady-state, oral	CILNIDIPINE plasma	Homo sapiens
2.8 h	5 mg single, oral	CILNIDIPINE plasma	Homo sapiens
4.9 h	10 mg single, oral	CILNIDIPINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.7%			CILNIDIPINE serum	Homo sapiens

Doses

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Dose	Population	Adverse events
20 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT	Other AEs: Skin eruption, Flushing of face...

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AEs

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AE	Significance	Dose	Population
Flushing of face	grade 1, 14%	20 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Skin eruption	grade 1, 7%	20 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT

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PubMed

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Title	Date	PubMed
Effect of cilnidipine, a novel dihydropyridine Ca++-channel antagonist, on N-type Ca++ channel in rat dorsal root ganglion neurons.	1997 Mar	9067302
Comparison of 24-hour blood pressure, heart rate, and autonomic nerve activity in hypertensive patients treated with cilnidipine or nifedipine retard.	1998 Aug	9700998
Renoprotective effect of the L/N-type calcium channel antagonist cilnidipine on puromycin aminonucleoside-induced nephrosis in rats.	2009	19338138

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Patents

Sample Use Guides

In Vivo Use Guide

Normally once daily 5 to 10 mg of cilnidipine after breakfast orally for adult patient. The dose can be increased or reduced according to the age and symptoms. If the above dose is not effective enough, the dose can be increased to 20 mg once daily. For severe hypertension, 10 to 20 mg of cilnidipine orally once daily after breakfast.

Route of Administration: Oral

In Vitro Use Guide

Cell viability of PC12 was not affected by low concentrations of cilnidipine up to 150 uM, but it was slightly decreased at 200 uM cilnidipine.

Substance Class	Chemical
Record UNII	97T5AZ1JIP
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

CILNIDIPINE

Official Name

English

CILNIDIPINE [JAN]

Common Name

English

cilnidipine [INN]

Common Name

English

SISCARD

Brand Name

English

FRC-8653

Code

English

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Classification Tree

Code System

Code

Dihydropyridine derivatives

WHO-VATC

QC08CA14

Dihydropyridine derivatives

WHO-ATC

C08CA14

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Code System

Code

Type

Description

MESH

C065927

PRIMARY

CAS

132203-70-4

PRIMARY

CAS

102106-21-8

NON-SPECIFIC STEREOCHEMISTRY

NCI_THESAURUS

C171754

PRIMARY

MERCK INDEX

m3548

PRIMARY

Merck Index

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Related Record

Type

Details


					OIC6NC9Q3P

VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL SUBUNIT ALPHA-1D

TARGET -> INHIBITOR


					S85436ZG85

CILNIDIPINE, (+)-

ENANTIOMER -> RACEMATE


					4LNU2SU262

CILNIDIPINE, (-)-

ENANTIOMER -> RACEMATE

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Related Record

Type

Details


					97T5AZ1JIP

CILNIDIPINE

ACTIVE MOIETY

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound