Linsidomine

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H10N4O2
Molecular Weight	170.1692
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[NH-]C1=C[N+](=NO1)N2CCOCC2

InChI

InChIKey=FKDHHVKWGRFRTG-UHFFFAOYSA-N

InChI=1S/C6H10N4O2/c7-6-5-10(8-12-6)9-1-3-11-4-2-9/h5,7H,1-4H2

HIDE SMILES / InChI

Molecular Formula	C6H11N4O2
Molecular Weight	171.1771
Charge	1
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8775048
Curator's Comment: description was created based on several sources, including https://www.drugs.com/international/linsidomine.html | https://www.ncbi.nlm.nih.gov/pubmed/1953615 | https://www.ncbi.nlm.nih.gov/pubmed/9458423 | https://www.ncbi.nlm.nih.gov/pubmed/26381495

Linsidomine (SIN-1, chemically 3-morpholinosydnonimin), is a vasodilator and antianginal drug. It is the direct hepatic metabolite of molsidomine. The dosage recommended by its manufacturer for its initial purpose, coronary angiography, is 0.4-1 mg. Contrary to molsidomine, which is widely used as an antianginal drug, linsidomine is used only for coronary angiography. The plasma half-life of Linsidomine is about 1 hour. Linsidomine is nonenzymatically metabolized to SIN-1A which spontaneously releases NO. NO, probably released directly from nonadrenergic, noncholinergic (NANC) nerves in the penis, is believed to cause smooth muscle relaxation by stimulating the soluble form of guanylate cyclase leading to an increase of intracellular cyclic guanosine 3',5' monophosphate (cGMP) with subsequent smooth muscle relaxation. Linsidomine also hyperpolarizes the cell membrane, making the smooth muscle less susceptible to adrenergic stimulation. NO further interacts with platelets when released intraluminally causing an increase in cGMP that decreases platelet aggregation and adhesion

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Short transient receptor potential channel 5 2 Target ID: CHEMBL1250411 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16998480	Activator 1430
nitric oxide 2 Target ID: nitric oxide Sources: https://www.ncbi.nlm.nih.gov/pubmed/8775048	Releasing Agent 8

Conditions

Condition	Modality	Targets	Highest Phase	Product
Angina 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8775048	Diagnostic		Approved 8429	Corvasal intracoronaire Approved Use Unknown
Unstable angina 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9458423	Primary		Not Provided 504	Corvasal intracoronaire Approved Use Unknown

PubMed

Title	Date	PubMed
Splenic B lymphocyte programmed cell death is prevented by nitric oxide release through mechanisms involving sustained Bcl-2 levels.	1995 Apr	7706495
Mediation by prostaglandins of the nitric oxide-induced neurogenic vasodilatation in rat skin.	1995 Nov	8581270
Expression of heme oxygenase isozyme mRNAs in the human brain and induction of heme oxygenase-1 by nitric oxide donors.	1996 Aug	8764571
Peroxynitrite modulates MnSOD gene expression in lung epithelial cells.	1998 Sep	9741582
Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors.	1999 Jul 15	10423162
Nitric oxide enhances the manganese superoxide dismutase-dependent suppression of proliferation in HT-1080 fibrosarcoma cells.	1999 Sep	10511315
Nitric oxide inhibits apoptosis via AP-1-dependent CD95L transactivation.	2000 May 1	10811113
The effect of the nitric oxide synthesis inhibitor L-NAME on amitriptyline-induced hypotension in rats.	2002	12126183
Dynamic and biphasic modulation of nitrosation reaction by superoxide dismutases.	2002 Aug 2	12135611
Peroxynitrite activates NF-E2-related factor 2/antioxidant response element through the pathway of phosphatidylinositol 3-kinase: the role of nitric oxide synthase in rat glutathione S-transferase A2 induction.	2002 Dec	12446173
Protection of myocytes from hypoxia-reoxygenation injury by nitric oxide is mediated by modulation of transforming growth factor-beta1.	2002 May 7	11994256
Metallothionein attenuates 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in dopaminergic neurons.	2003 Jun	12880480
Reactive nitrogen species block cell cycle re-entry through sustained production of hydrogen peroxide.	2003 Jun	12600834
PKC downstream of Pl3-kinase regulates peroxynitrite formation for Nrf2-mediated GSTA2 induction.	2004 Jul	15357004
Cisplatin upregulates mitochondrial nitric oxide synthase and peroxynitrite formation to promote renal injury.	2009 Jan 15	19038279
Neuroprotective effects of Cyperus rotundus on SIN-1 induced nitric oxide generation and protein nitration: ameliorative effect against apoptosis mediated neuronal cell damage.	2013 Jan	23174672

Patents

Sample Use Guides

In Vivo Use Guide

Recommended dose range is 0.4-1 mg per diagnostic procedure.

Route of Administration: Intracoronary

In Vitro Use Guide

HUVECs were pre-treated with 100 mkM SIN-1 (Linsidomine) or 100 mkM tempol (Sigma-Aldrich) for 1 h and then stimulated with 5 U/ml thrombin (Sigma-Aldrich) for 30 min. The amount of vWF released into the media was measured using a commercial enzyme-linked immunosorbent assay kit (Corgenix, Westminster, CO, USA).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:23:21 GMT 2023` Edited by `admin` on `Fri Dec 15 16:23:21 GMT 2023`
Record UNII	5O5U71P6VQ
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

Linsidomine

Official Name

English

Sydnonimine-1

Common Name

English

Linsidomine [WHO-DD]

Common Name

English

SIN1

Code

English

linsidomine [INN]

Common Name

English

3-MORPHOLINOSYDNONE IMINE

Systematic Name

English

SIN-1

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C45845