AMLODIPINE MALEATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C20H25ClN2O5.C4H4O4
Molecular Weight	524.948
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

OC(=O)\C=C/C(O)=O.CCOC(=O)C1=C(COCCN)NC(C)=C(C1C2=C(Cl)C=CC=C2)C(=O)OC

InChI

InChIKey=TZNOWAJJWCGILX-BTJKTKAUSA-N

InChI=1S/C20H25ClN2O5.C4H4O4/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21;5-3(6)1-2-4(7)8/h5-8,17,23H,4,9-11,22H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C20H25ClN2O5
Molecular Weight	408.876
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular mooth muscle cells than on cardiac muscle cells. Amlodipine is indicated for the treatment of hypertension and coronary artery disease.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated L-type calcium channel alpha-1C subunit 44	Antagonist 2,778		57.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 567	Primary	Approved 8,429	NORVASC
Coronary artery disease 48	Primary	Approved 8,429	NORVASC
Chagas disease 19	Primary	Preclinical	Unknown

C_max

Value	Dose	Analyte	Population
2.3 ng/mL	5 mg single, oral	AMLODIPINE plasma	Homo sapiens
3 μg/L	5 mg single, oral	AMLODIPINE plasma	Homo sapiens
5.9 μg/L	10 mg single, oral	AMLODIPINE plasma	Homo sapiens
10.4 μg/L	20 mg single, oral	AMLODIPINE plasma	Homo sapiens
3.5 ng/mL	5 mg single, oral	AMLODIPINE plasma	Homo sapiens
10.5 ng/mL	5 mg 1 times / day steady-state, oral	AMLODIPINE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
114 ng × h/mL	5 mg single, oral	AMLODIPINE plasma	Homo sapiens
187 μg × h/L	5 mg single, oral	AMLODIPINE plasma	Homo sapiens
238 μg × h/L	10 mg single, oral	AMLODIPINE plasma	Homo sapiens
464 μg × h/L	20 mg single, oral	AMLODIPINE plasma	Homo sapiens
169 ng × h/mL	5 mg single, oral	AMLODIPINE plasma	Homo sapiens
214 ng × h/mL	5 mg 1 times / day steady-state, oral	AMLODIPINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
48 h	5 mg single, oral	AMLODIPINE plasma	Homo sapiens
36 h	10 mg single, oral	AMLODIPINE plasma	Homo sapiens
37 h	20 mg single, oral	AMLODIPINE plasma	Homo sapiens
41 h	5 mg single, oral	AMLODIPINE plasma	Homo sapiens
47 h	5 mg 1 times / day steady-state, oral	AMLODIPINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
2%			AMLODIPINE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
75 mg single, oral (mean) Overdose	unhealthy, 42 years n = 1	Disc. AE: Sinus tachycardia, Metabolic acidosis...
10 mg 1 times / day steady, oral (min) Recommended	unhealthy, adult n = 1250	Disc. AE: Headache...
10 mg 1 times / day steady, oral Recommended	unhealthy, adult n = 268	DLT: Edema, Dizziness...
2.5 mg 1 times / day steady, oral Recommended	unhealthy, adult n = 275	DLT: Edema, Dizziness...
5 mg 1 times / day steady, oral Recommended	unhealthy, adult n = 296	DLT: Edema, Dizziness...

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AEs

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AE	Significance	Dose	Population
Hypocalcemia	1 patient Disc. AE	75 mg single, oral (mean) Overdose	unhealthy, 42 years n = 1
Metabolic acidosis	1 patient Disc. AE	75 mg single, oral (mean) Overdose	unhealthy, 42 years n = 1
Sinus tachycardia	1 patient Disc. AE	75 mg single, oral (mean) Overdose	unhealthy, 42 years n = 1
Headache	1.5% Disc. AE	10 mg 1 times / day steady, oral (min) Recommended	unhealthy, adult n = 1250
Edema	10.8% DLT	10 mg 1 times / day steady, oral Recommended	unhealthy, adult n = 268

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inhibitor 1,587	inhibitor 1,767	inhibitor 1,852	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP4 204 CYP1A1 110 CYP1A2 1,524 CYP2A6 707 CYP2B6 810 CYP2C19 1,478 CYP2E1 882 CYP3A5 73 CYP2C8 911 P-gp 1,461 BCRP 699 OATP1B1 788 OATP1B3 706 BSEP 402 MRP2 383 MRP3 157	CYP3A 191 CYP2B6 664 CYP3A5 395 P-gp 1,537

Drug as perpetrator

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Target	Modality	Activity
BCRP 773	inhibitor 3,277	moderate [IC50 11.3 uM]
BSEP 403	inhibitor 3,277	no [IC50 >133 uM]
MRP2 475	inhibitor 3,277	no [IC50 >133 uM]
MRP3 207	inhibitor 3,277	no [IC50 >133 uM]
MRP4 238	inhibitor 3,277	no [IC50 >133 uM]

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Drug as victim

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Target	Modality	Activity	Clinical evidence
CYP2B6 664	substrate 3,367	likely
CYP3A4 1,737	substrate 3,367	major
CYP3A 191	substrate 3,367	major	yes (co-administration study)
CYP3A5 395	substrate 3,367	yes	yes (pharmacogenomic study)
P-gp 1,537	substrate 3,367	yes	yes (pharmacogenomic study)

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2668	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2668
Selleck Chemicals	Amlodipine(Norvasc)	http://www.selleckchem.com/products/Amlodipine(Norvasc).html
eMolecules	901374	https://www.emolecules.com/cgi-bin/more?vid=901374

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PubMed

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Title	Date	PubMed
A double-blind evaluation of the effect of amlodipine on ambulatory blood pressure.	1991	1839434
24-hour blood pressure control with the once-daily calcium antagonist amlodipine.	1991	16296698
The unique binding properties of amlodipine: a long-acting calcium antagonist.	1991 Aug	1834847
Pharmacologic characterization of FR172516: a new combined calcium channel-blocking and beta-adrenoceptor-blocking agent.	1999 Apr	10218729
[Effects of benidipine hydrochloride (Coniel) on blood pressure, heart rate and plasma norepinephrine concentration in spontaneously hypertensive rats].	1999 May	10480159

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Patents

Sample Use Guides

In Vivo Use Guide

Adult recommended starting dose: 5 mg once daily with maximum dose 10 mg once daily. Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily. Pediatric starting dose: 2.5 mg to 5 mg once daily. Important Limitation: Doses in excess of 5 mg daily have not been studied.

Route of Administration: Oral

In Vitro Use Guide

amlodipine was effective against A. castellanii and B. mandrillaris at 250μM

Substance Class	Chemical
Record UNII	CQ27G2BZJM
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMLODIPINE MALEATE

Official Name

English

AMLODIPINE MALEATE [MART.]

Common Name

English

UK-48,340-11

Code

English

AMVAZ

Brand Name

English

3,5-PYRIDINEDICARBOXYLIC ACID, 2-((2-AMINOETHOXY)METHYL)-4-(2-CHLOROPHENYL)-1,4-DIHYDRO-6-METHYL-, 3-ETHYL 5-METHYL ESTER, (±)-, (Z)-2-BUTENEDIOATE (1:1)

Common Name

English

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Classification Tree

Code System

Code

Cation Channel Blocker

NCI_THESAURUS

C333

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Code System

Code

Type

Description

NCI_THESAURUS

C65230

PRIMARY

MERCK INDEX

m1757

PRIMARY

Merck Index

EVMPD

SUB00476MIG

PRIMARY

DRUG BANK

DBSALT001056

PRIMARY

PUBCHEM

6435922

PRIMARY

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Related Record

Type

Details


					12WW9T2ITA

LEVAMLODIPINE MALEATE

ENANTIOMER -> RACEMATE


					1J444QC288

AMLODIPINE

PARENT -> SALT/SOLVATE

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Related Record

Type

Details


					1J444QC288

AMLODIPINE

ACTIVE MOIETY

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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

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator