ISOSORBIDE DINITRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C6H8N2O8
Molecular Weight	236.1363
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

[H][C@]12OC[C@H](O[N+]([O-])=O)[C@@]1([H])OC[C@H]2O[N+]([O-])=O

InChI

InChIKey=MOYKHGMNXAOIAT-JGWLITMVSA-N

InChI=1S/C6H8N2O8/c9-7(10)15-3-1-13-6-4(16-8(11)12)2-14-5(3)6/h3-6H,1-2H2/t3-,4+,5-,6-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C6H8N2O8
Molecular Weight	236.1363
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Pentaerythritol tetranitrate is an organic nitrate that has been used for the treatment of angina pectoris. Upon administration, the drug undergoes exstensive metabolism to NO which causes vasodilation and the relaxation of smooth muscle cells. The compound belongs to a familiy of explosive substances and may be used accordingly.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
liberation of NO 18	Activator 1,430
Soluble guanylate cyclase 34	Activator 1,430	0.1 µM [EC50]
nitric oxide mediated signal transduction 1	Activator 1,430
Soluble guanylate cyclase 34	Activator 1,430
Atrial natriuretic peptide receptor A 19	Activator 1,430
Soluble guanylate cyclase 34	Activator 1,430
Soluble guanylate cyclase 34	Activator 1,430
Soluble guanylate cyclase 34	Activator 1,430

Conditions

Condition	Modality	Highest Phase	Product
Cancer 592	Primary	Preclinical	Unknown
Hypertensive crises 18	Primary	Approved 8,429	NIPRIDE
Heart failure 103	Primary	Approved 8,429	NIPRIDE
Pulmonary hypertension 30	Palliative	Approved 8,429	INOMAX
Angina pectoris 106	Primary	Approved 8,429	DILATRATE-SR
Angina pectoris 106	Primary	Approved 8,429	MONOKET
Angina pectoris 106	Primary	Approved 8,429	Unknown
Coronary heart disease 41	Primary	Basic research	Unknown
Angina 32	Primary	Approved 8,429	NITROSTAT
Myocardial infarction 121	Primary	Approved 8,429	NITROGLYCERIN
Hypertension 567	Primary	Approved 8,429	NITROGLYCERIN
Heart failure 103	Primary	Approved 8,429	NITROGLYCERIN
Angina pectoris 106	Primary	Approved 8,429	Metamine
Angina pectoris 106	Primary	Approved 8,429	PERITRATE

C_max

Value	Dose	Analyte	Population
187 ng/mL	20 mg single, oral	ISOSORBIDE DINITRATE plasma	Homo sapiens
356 ng/mL	20 mg single, intravenous	ISOSORBIDE MONONITRATE plasma	Homo sapiens
388 ng/mL	20 mg single, oral	ISOSORBIDE MONONITRATE plasma	Homo sapiens
557 ng/mL	60 mg 1 times / day steady-state, oral	ISOSORBIDE MONONITRATE plasma	Homo sapiens
1151 ng/mL	120 mg 1 times / day steady-state, oral	ISOSORBIDE MONONITRATE plasma	Homo sapiens
84 ng/mL	13 mg single, oral	GLYCERYL 1,2-DINITRATE plasma	Homo sapiens
1.7 pg/mL	800 μg single, sublingual	NITROGLYCERIN plasma	Homo sapiens
17 ng/mL	100 mg single, oral	PENTAERYTHRITOL DINITRATE plasma	Homo sapiens
7.5 ng/mL	100 mg single, oral	PENTAERYTHRITOL DINITRATE plasma	Homo sapiens
79 ng/mL	100 mg single, oral	PENTAERYTHRITOL MONONITRATE plasma	Homo sapiens
35 ng/mL	100 mg single, oral	PENTAERYTHRITOL MONONITRATE plasma	Homo sapiens
15 ng/mL	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
29.7 ng/mL	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
17.9 ng/mL	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
4.4 ng/mL	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
5.3 ng/mL	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
0.89 ng/mL/kg	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
0.03 ng/mL/kg	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
0.26 ng/mL/kg	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
0.08 ng/mL/kg	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
32 μg/L	16 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
37 μg/L	16 mg 1 times / day multiple, oral	MOLSIDOMINE plasma	Homo sapiens
8 μg/L	16 mg single, oral	LINSIDOMINE plasma	Homo sapiens
8 μg/L	16 mg 1 times / day multiple, oral	LINSIDOMINE plasma	Homo sapiens
32 μg/L	16 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
34 μg/L	16 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
8 μg/L	16 mg single, oral	LINSIDOMINE plasma	Homo sapiens
10 μg/L	16 mg single, oral	LINSIDOMINE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
1458 ng × h/mL	20 mg single, oral	ISOSORBIDE DINITRATE plasma	Homo sapiens
2647 ng × h/mL	20 mg single, intravenous	ISOSORBIDE MONONITRATE plasma	Homo sapiens
2524 ng × h/mL	20 mg single, oral	ISOSORBIDE MONONITRATE plasma	Homo sapiens
6979 ng × h/mL	60 mg 1 times / day steady-state, oral	ISOSORBIDE MONONITRATE plasma	Homo sapiens
14241 ng × h/mL	120 mg 1 times / day steady-state, oral	ISOSORBIDE MONONITRATE plasma	Homo sapiens
3380 ng × min/mL	13 mg single, oral	GLYCERYL 1,2-DINITRATE plasma	Homo sapiens
12.3 pg × min/mL	800 μg single, sublingual	NITROGLYCERIN plasma	Homo sapiens
106.5 μg × h/L	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
31.7 μg × h/L	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
12.2 μg × h/L	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
7.4 μg × h/L	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
17.54 ng × h/mL/kg	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
0.5 ng × h/mL/kg	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
0.46 ng × h/mL/kg	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
0.11 ng × h/mL/kg	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
311 ng × h/mL	16 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
423 ng × h/mL	16 mg 1 times / day multiple, oral	MOLSIDOMINE plasma	Homo sapiens
60 ng × h/mL	16 mg single, oral	LINSIDOMINE plasma	Homo sapiens
61 ng × h/mL	16 mg 1 times / day multiple, oral	LINSIDOMINE plasma	Homo sapiens
335 ng × h/mL	16 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
310 ng × h/mL	16 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
49 ng × h/mL	16 mg single, oral	LINSIDOMINE plasma	Homo sapiens
70 ng × h/mL	16 mg single, oral	LINSIDOMINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
303 min	20 mg single, oral	ISOSORBIDE DINITRATE plasma	Homo sapiens
4 h	20 mg single, intravenous	ISOSORBIDE MONONITRATE plasma	Homo sapiens
4 h	20 mg single, oral	ISOSORBIDE MONONITRATE plasma	Homo sapiens
6.2 h	60 mg 1 times / day steady-state, oral	ISOSORBIDE MONONITRATE plasma	Homo sapiens
6.2 h	120 mg 1 times / day steady-state, oral	ISOSORBIDE MONONITRATE plasma	Homo sapiens
50 min	13 mg single, oral	GLYCERYL 1,2-DINITRATE plasma	Homo sapiens
40 min	800 μg single, sublingual	NITROGLYCERIN plasma	Homo sapiens
2 min	single, intravenous	NITROPRUSSIDE plasma	Rattus norvegicus
4.5 h	100 mg single, oral	PENTAERYTHRITOL DINITRATE plasma	Homo sapiens
4.5 h	100 mg single, oral	PENTAERYTHRITOL DINITRATE plasma	Homo sapiens
10.5 h	100 mg single, oral	PENTAERYTHRITOL MONONITRATE plasma	Homo sapiens
10.5 h	100 mg single, oral	PENTAERYTHRITOL MONONITRATE plasma	Homo sapiens
1.6 h	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
1.9 h	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
1.2 h	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
1.8 h	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
1 h	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
13.1 h	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
7.5 h	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
1.2 h	2 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
1 h	2 mg single, oral	LINSIDOMINE plasma	Homo sapiens
12 h	16 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
12 h	16 mg 1 times / day multiple, oral	MOLSIDOMINE plasma	Homo sapiens
10 h	16 mg single, oral	LINSIDOMINE plasma	Homo sapiens
12 h	16 mg 1 times / day multiple, oral	LINSIDOMINE plasma	Homo sapiens
9.7 h	16 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
8.2 h	16 mg single, oral	MOLSIDOMINE plasma	Homo sapiens
6.6 h	16 mg single, oral	LINSIDOMINE plasma	Homo sapiens
5.8 h	16 mg single, oral	LINSIDOMINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
100%			ISOSORBIDE DINITRATE plasma	Homo sapiens
100%	2 mg single, oral		MOLSIDOMINE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
75 mg 3 times / day multiple, oral Recommended\|MTD	unhealthy, mean age 57 years	Other AEs: Headache, Dizziness...
75 mg 3 times / day multiple, oral Recommended\|MTD	unhealthy, mean age 57 years	Disc. AE: Chest pain, Heart arrest...
75 mg 3 times / day multiple, oral Recommended\|MTD	unhealthy, mean age 57 years	Other AEs: Chest pain, Heart failure...
75 mg 3 times / day multiple, oral Recommended\|MTD	unhealthy, mean age 57 years	Disc. AE: Asthenia, Headache...
240 mg 1 times / day steady, oral Highest studied dose	unhealthy, adult	Other AEs: Headache...

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AEs

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AE	Significance	Dose	Population
Nausea	10%	75 mg 3 times / day multiple, oral Recommended\|MTD	unhealthy, mean age 57 years
Asthenia	14%	75 mg 3 times / day multiple, oral Recommended\|MTD	unhealthy, mean age 57 years
Tachycardia	2%	75 mg 3 times / day multiple, oral Recommended\|MTD	unhealthy, mean age 57 years
Amblyopia	3%	75 mg 3 times / day multiple, oral Recommended\|MTD	unhealthy, mean age 57 years
Hyperlipidemia	3%	75 mg 3 times / day multiple, oral Recommended\|MTD	unhealthy, mean age 57 years

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737	substrate 1,037	substrate 1,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1,461 MRP2 383 K+ channels 70 Ca2+ channels 57 ALDH2 19	ALDH2 19 CYP1A2 1,054 CYP2A6 543 CYP2E1 667 CYP4A11 119	OCT1 35

Drug as perpetrator

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Target	Modality	Activity
ALDH2 19	inhibitor 3,277	no
K+ channels 70	inhibitor 3,277	no
Ca2+ channels 60	inhibitor 3,277	yes
MRP2 475	inhibitor 3,277	yes
OCT1 543	inducer 1,573	yes

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Drug as victim

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Target	Modality	Activity
CYP3A4 1,737	substrate 3,367	major
CYP1A2 1,054	substrate 3,367	minor
CYP2A6 543	substrate 3,367	minor
CYP2C9 1,037	substrate 3,367	minor
CYP2D6 1,217	substrate 3,367	minor

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6061	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6061
ChemicalBook	CB2226929	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2226929
eMolecules	30154680	https://www.emolecules.com/cgi-bin/more?vid=30154680
eMolecules	33507015	https://www.emolecules.com/cgi-bin/more?vid=33507015
eMolecules	36753592	https://www.emolecules.com/cgi-bin/more?vid=36753592

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PubMed

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Title	Date	PubMed
Effect of alterations of arterial blood pressure and heart rate on segmental dyskinesis during acute myocardial ischemia and following coronary reperfusion.	1975 Jan	1078794
[The effects of sodiumnitroprusside and trimethaphan induced hypotension on haemodynamics and myocardial oxygen consumption (author's transl)].	1976 Jan	1259127
Positive inotropy contributes to the hemodynamic mechanism of action of flosequinan (BTS 49465) in the intact dog.	1990 Jun	1694912
Features of the acute hypotensive action of carvedilol and its ameliorating effect on myocardial ischemia.	1991	1721975
Rat renal papillary release of hypotensive substances in vitro.	1991 Aug	1655886

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Sample Use Guides

In Vivo Use Guide

mice were treated three times a week for 3 weeks with intravenous tail vein injections of either vehicle (2.25% Pluronic P123 in PBS) or JS-K (6 μmol/kg in the vehicle).

Route of Administration: Intravenous

In Vitro Use Guide

Human U87 cells (HTB-14), fibroblasts (CRL-1634), and astrocytes (CRL-8621; ATCC) were cultured in Dulbecco’s Minimal Essential Eagle Medium (DMEM; Gibco, USA) supplemented with 10% fetal calf serum (FCS) and penicillin (100U/mL)/streptomycin (100mg/mL) under normoxic conditions (95% air, 5% CO2, and 37°C). The nitric oxide donor JS-K (O2-(2.4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium1,2-diolate, CAS 7054 32-12-8) was dissolved in 100% dimethyl sulfoxide (DMSO) in a concentration of 5.2mM. U87 was incubated with JS-K doses of 0–15µM for 4 h. The JS-K solvent control (DMSO≤1%) was adjusted to the highest JS-K concentration used in these experiments. A cesium source emitting γ-radiation was used for radiotherapy (RT; 3×2Gy) with a 24-h interval between each RT dose (Isotopen Diagnostik CIS, Germany).

Substance Class	Chemical
Record UNII	IA7306519N
Record Status	`Validated (UNII)`
Record Version

Related Record	Type
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Name

Type

Language

ISOSORBIDE DINITRATE

Official Name

English

ISOSORBIDE DINITRATE [MART.]

Common Name

English

isosorbide dinitrate [INN]

Common Name

English

C01DA08

Code

English

ISOSORBIDE DINITRATE [USAN]

Common Name

English

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Classification Tree

Code System

Code

Agent Affecting Cardiovascular System

NCI_THESAURUS

C29707

Muscle relaxants

WHO-VATC

QC05AE02

Nitric Acid

NDF-RT

N0000007647

Nitric Acid

NDF-RT

N0000007647

Vascular Tone Alteration

NDF-RT

N0000009909

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Code System

Code

Type

Description

NSC

80038

PRIMARY

FDA UNII

IA7306519N

PRIMARY

ChEMBL

CHEMBL6622

PRIMARY

PUBCHEM

6883

PRIMARY

NCI_THESAURUS

C29134

PRIMARY

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Related Record

Type

Details

DILUTED ISOSORBIDE DINITRATE

SUB_CONCEPT->SUBSTANCE

Amount:


					IA7306519N

ISOSORBIDE DINITRATE

BASIS OF STRENGTH->SUBSTANCE

Interaction Type:

ASSAY (HPLC)

Qualification:

EP

Amount:


					IA7306519N

ISOSORBIDE DINITRATE

BASIS OF STRENGTH->SUBSTANCE

Comments:

It usually contains approximately 25 percent of isosorbide dinitrate

Interaction Type:

ASSAY (HPLC)

Qualification:

USP

Amount:

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Related Record

Type

Details


					21BMF8FI0K

ISOSORBIDE 2-NITRATE

METABOLITE -> PARENT

Interaction Type:

MINOR

Qualification:

PLASMA

Amount:


					31C4KY9ESH

NITRIC OXIDE

METABOLITE ACTIVE -> PRODRUG

Amount:

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Related Record

Type

Details


					LX1OH63030

ISOSORBIDE MONONITRATE

PARENT -> IMPURITY

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:


					T93E9Y2844

NITRATE ION

IMPURITY -> PARENT

Comments:

calculated as potassium nitrate

Interaction Type:

CHROMATOGRAPHIC PURITY (TLC)

Qualification:

EP

Amount:


					LX1OH63030

ISOSORBIDE MONONITRATE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:


					21BMF8FI0K

ISOSORBIDE 2-NITRATE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

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Related Record

Type

Details


					31C4KY9ESH

NITRIC OXIDE

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount	Referenced Substance	Defining	Parameters	References
Volume of Distribution	PHARMACOKINETIC

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator