LIGUSTRAZINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H12N2.ClH
Molecular Weight	172.655
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC1=NC(C)=C(C)N=C1C

InChI

InChIKey=RQKFOGXUTRDQPB-UHFFFAOYSA-N

InChI=1S/C8H12N2.ClH/c1-5-6(2)10-8(4)7(3)9-5;/h1-4H3;1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24660601 | https://www.ncbi.nlm.nih.gov/pubmed/27523814 | https://www.ncbi.nlm.nih.gov/pubmed/27668034

Ligustrazine (tetramethylpyrazine) is a bioactive ingredient extracted from the widely-used Chinese herb, Chuanxiong. It inhibits of platelet aggregation, enhances of vessel dilation, increases cerebral blood flow and possesses neuroprotective properties. The injection solution of ligustrazine has been used especially in China to treat ischemic stroke, coronary heart disease, diabetic nephropathy, and knee osteoarthritis. Ligustrazine was also evaluated in clinical as a remedy for pressure sores, as a salvage agent for patients with non-Hodgkin's lymphoma, as a treatment for bronchial asthma and vertebrobasilar insufficiency.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Platelet activation 4 Target ID: map04611 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9526946	Inhibitor 8504
Voltage-gated L-type calcium channel 95 Target ID: CHEMBL2095229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23058991	Inhibitor 8504
nitric oxide production involved in inflammatory response 17 Target ID: GO:0002537 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27668034	Activator 1447

Conditions

Condition	Modality	Highest Phase	Product
Osteoarthritis of knee 23 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16951526	Primary	Approved 8583	Unknown Approved Use Unknown
Ischemic stroke 35 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24660601	Primary	Approved 8583	Unknown Approved Use Unknown
Coronary heart disease 43 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18198639	Primary	Approved 8583	Unknown Approved Use Unknown
Diabetic nephropathy 37 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22298446	Primary	Approved 8583	Unknown Approved Use Unknown
Bronchial asthma 50 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18853120	Primary	Not Provided 511	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1109.78 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29882510/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LIGUSTRAZINE PHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1284.26 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23514701/	108 mg single, oral dose: 108 mg route of administration: Oral experiment type: SINGLE co-administered:	LIGUSTRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
309.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23514701/	250 mg single, transdermal dose: 250 mg route of administration: Transdermal experiment type: SINGLE co-administered:	LIGUSTRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
326.13 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23514701/	250 mg 1 times / day multiple, transdermal dose: 250 mg route of administration: Transdermal experiment type: MULTIPLE co-administered:	LIGUSTRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status:
613.44 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23514701/	54 mg 3 times / day multiple, oral dose: 54 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LIGUSTRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status:

AUC

Value	Dose	Analyte	Population
1786.29 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29882510/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LIGUSTRAZINE PHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2715.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23514701/	108 mg single, oral dose: 108 mg route of administration: Oral experiment type: SINGLE co-administered:	LIGUSTRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3313.58 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23514701/	250 mg single, transdermal dose: 250 mg route of administration: Transdermal experiment type: SINGLE co-administered:	LIGUSTRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3753.91 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23514701/	250 mg 1 times / day multiple, transdermal dose: 250 mg route of administration: Transdermal experiment type: MULTIPLE co-administered:	LIGUSTRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status:
1187.89 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23514701/	54 mg 3 times / day multiple, oral dose: 54 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LIGUSTRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status:

T_1/2

Value	Dose	Analyte	Population
1.69 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29882510/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LIGUSTRAZINE PHOSPHATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.49 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23514701/	108 mg single, oral dose: 108 mg route of administration: Oral experiment type: SINGLE co-administered:	LIGUSTRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.61 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23514701/	54 mg 3 times / day multiple, oral dose: 54 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LIGUSTRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status:

F_unbound

Value	Dose	Co-administered	Analyte	Population
34.15% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21213541/			LIGUSTRAZINE PHOSPHATE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
1800 mg single, intravenous Highest studied dose Dose: 1800 mg Route: intravenous Route: single Dose: 1800 mg Sources: https://pubmed.ncbi.nlm.nih.gov/32864754/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/32864754/	Sources: https://pubmed.ncbi.nlm.nih.gov/32864754/
1400 mg 2 times / day multiple, intravenous Dose: 1400 mg, 2 times / day Route: intravenous Route: multiple Dose: 1400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32864754/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/32864754/	Sources: https://pubmed.ncbi.nlm.nih.gov/32864754/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	inhibitor 2438 substrate 1193	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 550 CYP1A2 2153 CYP19A1 429 CYP2C19 2057 MRP5 31 MRP2 499 P-gp 1741 MRP3 246	CYP1A2 1197

Drug as perpetrator

Target	Modality	Activity
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDMwMzY5NyJ9fQ==	no [IC50 >1000 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/14296#section=BioAssay-Results Page: 126.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/14296#section=BioAssay-Results Page: 158.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/14296#section=BioAssay-Results Page: 159.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/14296#section=BioAssay-Results Page: 159.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/14296#section=BioAssay-Results Page: 160.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/25073399/	weak
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/14296#section=BioAssay-Results Page: 4.0	yes [IC50 35.5742 uM]
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19956884/	yes
MRP3 326	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19956884/	yes
MRP5 80	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19956884/	yes
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19956884/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24961110/	major
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24961110/	major
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24961110/	major

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/14296#section=BioAssay-Results Page: 159.0

PubMed

Title	Date	PubMed
Liquid chromatography-mass spectrometry method for determination of tetramethylpyrazine and its metabolite in dog plasma.	2004-12-25	15556542
Tetramethylpyrazine reduces ischemic brain injury in rats.	2004-11-30	15531085
[Effects of combination therapy of rehin and tetramethylpyrazine on experimental hepatic fibrosis induced by tetrachloride].	2004-11	15623384
[Study on ligustrazine in reversing multidrug resistance of HepG2/ADM cell in vitro].	2004-10	15631086
[Protective effect of tetramethylpyrazine and L-arginine on rats with acute myocardial infarction].	2004-10	15553826
[Effect of tetramethylpyrazine on lipopolysaccharides induced macrophage cyclo-oxidase-2 expression and apoptosis of cardiac myocytes].	2004-10	15553825
The electrochemistry and determination of Ligustrazine hydrochloride.	2004-10	15322795
Improvement of barrier function and stimulation of colonic epithelial anion secretion by Menoease Pills.	2004-09-01	15300895
Effect of ligustrazine on ischemia-reperfusion injury in murine kidney.	2004-09	15518708
Protective effect of tetramethylpyrazine on learning and memory function in D-galactose-lesioned mice.	2004-09	15506643
The protective effects of ligustrazine on ischemia-reperfusion and DPPH free radical-induced myocardial injury in isolated rat hearts.	2004-09	15386191
Preparative isolation and purification of chuanxiongzine from the medicinal plant Ligusticum chuanxiong by high-speed counter-current chromatography.	2004-08-27	15460256
[Experimental study on prevention and treatment of bronchial asthma by compound Chinese herbal monomer recipe].	2004-08	15366597
[Effects of ligustrazine on expression of PECAM-1/CD31 and hematopoietic reconstitution in syngenic bone marrow transplantation of mice].	2004-08	15363138
[Effect of chuanxiongzine on the relaxation of isolated rabbit corpus cavernosum tissues].	2004-08	15362533
[Study on the interactions between four components in Ligusticum chuanxiong rhizome and acceptors on cardiac muscle membrane].	2004-07	15503774
Differential Cl- and HCO3- mediated anion secretion by different colonic cell types in response to tetromethylpyrazine.	2004-06-15	15188502
[The effect of ligustrazine on the expression of CD44 in bone marrow of bone marrow transplantation mice].	2004-06	15228650
[Effect of ligustrazine on expressions of basic fibroblast growth factor and its receptor in bone marrow of mice with acute radiation injury].	2004-05	15199631
[Cardiac hemodynamics after suprarenal ligation of the inferior vena cava and the resection of the right kidney or injection of ligustrazine in rats].	2004-05	15142439
[Effect of ligustrazine on the expression of LFA-1 and ICAM-1 in bone marrow transplantation recipient mice].	2004-04	15157328
Effects of electroacupuncture plus intra-carotid drug injection on rheoencephalogram in patients with cerebral infarction.	2004-03	15119167
[Progress of the study on effective integredients from Chinese herbal medicine in anti-tumor metastasis].	2004-02	15015459
[Effect of Ligustrazine on the expression of vascular endothelial growth factor in bone marrow stromal cells of radiation injured mice].	2004-02	14989777
Preparation of cardiovascular disease-related genes microarray and its application in exploring ligustrazine-induced changes in endothelial gene expression.	2004-01-30	15520497
Studies on the aroma of cupuassu liquor by headspace solid-phase microextraction and gas chromatography.	2004-01-30	14753678
Effect of tetramethylpyrazine on acute nociception mediated by signaling of P2X receptor activation in rat.	2004-01-09	14672814
[Effect of tetromethylpyrazine and aminoguanidine on expression of vascular endothelial growth factor in kidney of diabetic rats].	2004-01	15339503
Nitric oxide-mediated vasorelaxation by Rhizoma Ligustici wallichii in isolated rat thoracic aorta.	2004-01	14971721
[Chemical profiles of methylpyrazines contained in commercially available natto].	2004-01	14768353
The oxygen radical generator pyrogallol impairs cardiomyocyte contractile function via a superoxide and p38 MAP kinase-dependent pathway: protection by anisodamine and tetramethylpyrazine.	2004	15531780
Inhibitory effects of ligustrazine, a modulator of thromboxane-prostacycline-nitric oxide balance, on renal injury in rats with passive Heyman nephritis.	2004	15528953
Pickles, pectin, and penicillin.	2004	15487928
Effect of ligustrazine on the expression of LFA-1, ICAM-1 following bone marrow transplantation in mice.	2004	15315336
Inhibition of shear-induced platelet aggregation in rat by tetramethylpyrazine and salvianolic acid B.	2004	15310944
Basolateral membrane mechanisms involved in ligustrazine-stimulated anion secretion in rat distal colon.	2003-12-25	14695481
[Protective effect of ligustrazine on insulin resistance after local cerebral ischemia of rat].	2003-12	15617507
Tetramethylpyrazine elicits disparate responses in cardiac contraction and intracellular Ca(2+) transients in isolated adult rat ventricular myocytes.	2003-11	14746828
Effect of tetramethylpyrazine on exocrine pancreatic and bile secretion.	2003-11	14606085
[Effect of ligustrazine on cell cycle and prostacyclin of injured vascular endothelial cells induced by hypoxia and lack of glucose].	2003-10	14768390
[Effect of tetramethylpyrazine on learning, memory and cholinergic system in D-galactose-lesioned mice].	2003-10	14650157
Effect of tetramethylpyrazine on potassium channels to lower calcium concentration in cultured aortic smooth muscle cells.	2003-10	14516420
[Ligustrazine and Salvia miltiorrhiza injection solution in complementary therapy of pregnancy-induced hypertension: clinical analysis of 60 cases].	2003-09	13129738
[Effect of ligustrazine on proliferative glomerulonephritis].	2003-08	14649206
[Effects of tetramethylpyrazine on cytosolic free calcium concentration in penis corpus cavernsum smooth muscle cells in rabbits].	2003-08	14513636
[Effect of ligustrazine on the expression of Bcl-2 protein and apoptosis in rabbit articular chondrocytes in monolayer culture].	2003-06	14653072
[Study on the effects of tetramethylpyrazine on tumor cells: survey and prospects].	2003-04	15171214
The effects of Ligustrazine on the expression of bFGF and bFGFR in bone marrow in radiation injured mice.	2003	15015632
[Effects of ligustrazine on blood vessels and blood components].	2002-02	14740662
[Advances in the study on transdermal permeation of active elements of natural drugs in vitro].	2002-01	14730719

Patents

Sample Use Guides

In Vivo Use Guide

In a clinical trial for the treatment of pressure sores, ligustrazine was applied with a transdermal patch. For treatment of bronchial asthma, ligustrazine was administered by inhalation. For treatment of vertebrobasilar insufficiency, ligustrazine was administered intravenously (80 mg of ligustrazine in 250 ml of 5% glucose or 0.9% normal saline for 15 days).

Route of Administration: Other

In Vitro Use Guide

Tetramethylpyrazine was tested for its antiplatelet activities in human platelet suspensions. In human platelets, tetramethylpyrazine (0.5-1.5 mM) dose-dependently inhibited platelet aggregation, as measured by a turbidimetric method.

Name

Type

Language

Ligustrazine hydrochloride [WHO-DD]

Preferred Name

English

LIGUSTRAZINE HYDROCHLORIDE

Common Name

English

PYRAZINE, 2,3,5,6-TETRAMETHYL-, HYDROCHLORIDE (1:1)

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID20997867