SIPATRIGINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H16Cl3N5
Molecular Weight	372.68
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCN(CC1)C2=NC(N)=C(C=N2)C3=C(Cl)C(Cl)=CC(Cl)=C3

InChI

InChIKey=PDOCBJADCWMDGL-UHFFFAOYSA-N

InChI=1S/C15H16Cl3N5/c1-22-2-4-23(5-3-22)15-20-8-11(14(19)21-15)10-6-9(16)7-12(17)13(10)18/h6-8H,2-5H2,1H3,(H2,19,20,21)

HIDE SMILES / InChI

Description
Sources: https://www.smr.org.uk/smr/Archive/Newsletters/Downloads/2002-01.pdf | https://www.ncbi.nlm.nih.gov/pubmed/17703894 | https://www.ncbi.nlm.nih.gov/pubmed/12706458

Sipatrigine (BW 619C89), a blocker of neuronal Na+ and Ca2+ channels, has neuroprotective efficacy. This drug was in phase II studies in stroke patients who received iv infusions of sipatrigine. The main adverse events observed were hallucinations and vomiting. The Phase II trial was terminated when Glaxo merged with Wellcome and a decision was made to develop the NMDA (glycine site) receptor antagonist gavestinel (from Glaxo), which showed no efficacy in a randomized, double blind, placebo- controlled trial. It was also assumed, that sipatrigine could have therapeutic potential for major depression and bipolar depression through antagonism of the two-pore-domain K+ channel TREK-1. but further evaluation of its antidepressant therapeutic and toxic effects in animal models is needed before clinical application.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-dependent R-type calcium channel subunit alpha-1E 3 Target ID: Q15878 Gene ID: 777.0 Gene Symbol: CACNA1E Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12706458	Inhibitor 8297
Potassium channel subfamily K member 2 6 Target ID: O95069\|\|\|Q9NRT2 Gene ID: 3776.0 Gene Symbol: KCNK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17703894	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Major depression 8 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17703894	Primary	Basic research	Unknown Approved Use Unknown
Bipolar depression 9 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17703894	Primary	Basic research	Unknown Approved Use Unknown
Acute stroke 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11070372	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
33 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.25 mg/kg 3 times / day multiple, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
51 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.5 mg/kg 3 times / day multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
89 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.75 mg/kg 3 times / day multiple, intravenous dose: 0.75 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
120 mg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1 mg/kg 3 times / day multiple, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
117 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1.25 mg/kg 3 times / day multiple, intravenous dose: 1.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
269 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1.25 mg/kg 3 times / 3 days multiple, intravenous dose: 1.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
266 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1 mg/kg 3 times / day multiple, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
370 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.75 mg/kg 3 times / day multiple, intravenous dose: 0.75 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
95 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.25 mg/kg 3 times / day multiple, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
157 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.5 mg/kg 3 times / day multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
215 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.25 mg/kg 3 times / day multiple, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
304 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.5 mg/kg 3 times / day multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
441 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.75 mg/kg 3 times / day multiple, intravenous dose: 0.75 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
741 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1 mg/kg 3 times / day multiple, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
840 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1.25 mg/kg 3 times / day multiple, intravenous dose: 1.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1370 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1.25 mg/kg 3 times / 3 days multiple, intravenous dose: 1.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1363 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1 mg/kg 3 times / day multiple, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2406 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.75 mg/kg 3 times / day multiple, intravenous dose: 0.75 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
321 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.25 mg/kg 3 times / day multiple, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
545 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.5 mg/kg 3 times / day multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
61 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.25 mg/kg 3 times / day multiple, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
58 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.5 mg/kg 3 times / day multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
74 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.75 mg/kg 3 times / day multiple, intravenous dose: 0.75 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1 mg/kg 3 times / day multiple, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
33 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1.25 mg/kg 3 times / day multiple, intravenous dose: 1.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	78C90 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1.25 mg/kg 3 times / 3 days multiple, intravenous dose: 1.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	1 mg/kg 3 times / day multiple, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.75 mg/kg 3 times / day multiple, intravenous dose: 0.75 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.25 mg/kg 3 times / day multiple, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8799514	0.5 mg/kg 3 times / day multiple, intravenous dose: 0.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	SIPATRIGINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
ApexBio Technology	B7573	https://www.apexbt.com/catalogsearch/result/?q=B7573
AstaTech	C14558	http://astatechinc.com/CPSResult.php?CRNO=C14558
BLD Pharm	BD136282	http://www.bldpharm.com/search/Search.html?keyword=BD136282
BOC Sciences	130800-90-7	http://www.bocsci.com/description.asp?cas=130800-90-7
Chem Scene	CS-0028364	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0028364
Lab Seeker	SC-47621	http://www.labseeker.com/search.php?keywords=SC-47621&category=0
LabSeeker	SC-47621	http://www.labseeker.com/search.php?keywords=SC-47621&category=0
MedChem Express	HY-108335	https://www.medchemexpress.com/search.html?q=HY-108335&ft=&fa=&fp=
MolPort	MolPort-023-277-047	https://www.molport.com/shop/molecule-link/MolPort-023-277-047
MuseChem	R036109	https://www.musechem.com/product/R036109.html
Princeton BioMolecular Research	PBMR221741	http://www.princetonbio.com/order_online?common_id=PBMR221741
Tocris	4044	https://www.tocris.com/search.php?Type=QuickSearch&Value=4044
Toronto Research Chemicals	S435050	https://www.trc-canada.com/product-detail/?CatNum=S435050
eMolecules	44466206	https://orderbb.emolecules.com/search/#?query=44466206
mcule	MCULE-2137595176	https://mcule.com/MCULE-2137595176/

PubMed

Title	Date	PubMed
BW619C89, a glutamate release inhibitor, protects against focal cerebral ischemic damage.	1993 Jul	8100654

Patents

Sample Use Guides

In Vivo Use Guide

acute stroke: Patients within 12 h of clinically diagnosed stroke were randomized to placebo or sipatrigine at total doses of 10, 18, 27, or 36 mg/kg by continuous intravenous infusion over 65 h. Pharmacokinetic and routine laboratory analyses were undertaken. The outcome at 30 days or 3 months was assessed by Barthel and Rankin scores.

Route of Administration: Intravenous

In Vitro Use Guide

It was studied the effect of BW619C89 (sipatrigine) on neurotransmitter release (endogenous amino acids, gamma-aminobutyric acid, and acetylcholine) from slices of rat brain cerebral cortex in vitro. It was shown, BW619C89 inhibited veratrine- (but not potassium-) evoked release of both endogenous glutamate and aspartate from rat cerebral cortex slices with IC50 values of approximately 5 microM. BW619C89 was approximately 10-fold less potent to inhibit veratrine-evoked 3H-gamma-aminobutyric acid release (IC50 = 51 microM), fourfold less potent to inhibit 3H-acetylcholine release (IC50 = 21 microM), and at 10 microM had only weak activity at excitatory amino acid (N-methyl-D-aspartate, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) binding sites. Thus was concluded, that BW619C89 might provide an alternative to excitatory amino acid receptor antagonists in the treatment of focal cerebral ischemia and stroke.

Name

Type

Language

SIPATRIGINE

Official Name

English

619C89

Code

English

Sipatrigine [WHO-DD]

Common Name

English

619-C-89

Code

English

sipatrigine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1509