TICLOPIDINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H14ClNS.ClH
Molecular Weight	300.247
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.ClC1=C(CN2CCC3=C(C2)C=CS3)C=CC=C1

InChI

InChIKey=MTKNGOHFNXIVOS-UHFFFAOYSA-N

InChI=1S/C14H14ClNS.ClH/c15-13-4-2-1-3-11(13)9-16-7-5-14-12(10-16)6-8-17-14;/h1-4,6,8H,5,7,9-10H2;1H

HIDE SMILES / InChI

Molecular Formula	C14H14ClNS
Molecular Weight	263.786
Charge	0
Count

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

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/19-979S018_Ticlid_prntlbl.pdf

Ticlopidine (trade name Ticlid) is an antiplatelet drug in the thienopyridine family which is an adenosine diphosphate (ADP) receptor inhibitor. Ticlopidine is a prodrug that is metabolized to an as yet undetermined metabolite that acts as a platelet aggregation inhibitor. Inhibition of platelet aggregation causes a prolongation of bleeding time. In its prodrug form, ticlopidine has no significance in vitro activity at the concentrations attained in vivo. The active metabolite of ticlopidine prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. It is proposed that the inhibition involves a defect in the mobilization from the storage sites of the platelet granules to the outer membrane. No direct interference occurs with the GPIIb/IIIa receptor. As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation. Ticlopidine is FDA approved for the prevention of strokes and, when combined with aspirin, for patients with a new coronary stent to prevent closure. There are also several off-label uses, including acute treatment of myocardial infarction and unstable angina, peripheral vascular disease, prevention of myocardial infarctions, diabetic retinopathy, and sickle cell disease. The most serious side effects associated with ticlopidine are those that affect the blood cells, although these life-threatening complications are relatively rare.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
platelet aggregation 76 Target ID: GO:0070527 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/19-979S018_Ticlid_prntlbl.pdf	Inhibitor 8297
Purinergic receptor P2Y12 23 Target ID: CHEMBL2001 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15852221	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Thrombotic stroke 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/19-979S018_Ticlid_prntlbl.pdf	Preventing		Approved 8429	TICLID Approved Use Ticlopidine hydrochloride tablets are indicated: to reduce the risk of thrombotic stroke (fatal or nonfatal) in patients who have experienced stroke precursors, and in patients who have had a completed thrombotic stroke. Because ticlopidine is associated with a risk of life-threatening blood dyscrasias including thrombotic thrombocytopenic purpura (TTP), neutropenia/agranulocytosis and aplastic anemia (see BOX WARNING and WARNINGS ), ticlopidine should be reserved for patients who are intolerant or allergic to aspirin therapy or who have failed aspirin therapy. as adjunctive therapy with aspirin to reduce the incidence of subacute stent thrombosis in patients undergoing successful coronary stent implantation (see CLINICAL TRIALS ). Launch Date 1991
Coronary artery disease 48 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/19-979S018_Ticlid_prntlbl.pdf	Preventing		Approved 8429	TICLID Approved Use Ticlopidine hydrochloride tablets are indicated: to reduce the risk of thrombotic stroke (fatal or nonfatal) in patients who have experienced stroke precursors, and in patients who have had a completed thrombotic stroke. Because ticlopidine is associated with a risk of life-threatening blood dyscrasias including thrombotic thrombocytopenic purpura (TTP), neutropenia/agranulocytosis and aplastic anemia (see BOX WARNING and WARNINGS ), ticlopidine should be reserved for patients who are intolerant or allergic to aspirin therapy or who have failed aspirin therapy. as adjunctive therapy with aspirin to reduce the incidence of subacute stent thrombosis in patients undergoing successful coronary stent implantation (see CLINICAL TRIALS ). Launch Date 1991

C_max

Value	Dose	Co-administered	Analyte	Population
365.3 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12419644	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		TICLOPIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
1053.9 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12419644	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		TICLOPIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.46 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12419644	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		TICLOPIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/75161_Ticlopidine%20Hydrochloride_Prntlbl.pdf			TICLOPIDINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18033957/	unhealthy, 64.7 n = 578 Health Status: unhealthy Condition: stroke Age Group: 64.7 Sex: M+F Population Size: 578 Sources: https://pubmed.ncbi.nlm.nih.gov/18033957/	Other AEs: Leukopenia, Neutropenia... Other AEs: Leukopenia (4 patients) Neutropenia (14 patients) Aspartate aminotransferase increased (13 patients) ALT increased (36 patients) Gamma GT increased (54 patients) ALP increased (2 patients) Cerebral hemorrhage (1 patient) Gastric ulcer hemorrhage (1 patient) Melena (1 patient) Epistaxis (2 patients) Rash (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/18033957/
250 mg 2 times / day multiple, oral Recommended Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20704700/	unhealthy, 70 n = 1 Health Status: unhealthy Condition: stroke Age Group: 70 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20704700/	Disc. AE: Agranulocytosis, AST increased... AEs leading to discontinuation/dose reduction: Agranulocytosis (1 patient) AST increased (1 patient) ALT increased (1 patient) Gamma GT increased (1 patient) ALP increased (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/20704700/
250 mg 2 times / day multiple, oral Recommended Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: https://pdf.hres.ca/dpd_pm/00015633.PDF	unhealthy, adult n = 2048 Health Status: unhealthy Condition: stroke Age Group: adult Population Size: 2048 Sources: https://pdf.hres.ca/dpd_pm/00015633.PDF	Disc. AE: Diarrhea, Nausea... AEs leading to discontinuation/dose reduction: Diarrhea (12.5%) Nausea (7%) Dyspepsia (7%) Rash (5.1%) GI pain (3.7%) Neutropenia (2.4%) Purpura (2.2%) Vomiting (1.9%) Flatulence (1.5%) Pruritus (1.3%) Dizziness (1.1%) Anorexia (1%) Sources: https://pdf.hres.ca/dpd_pm/00015633.PDF

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP1A2 1524 CYP2E1 882 CYP3A 214 CYP2B6 810	OATP2B1 104 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP3A5 395 CYP2J2 56 CES1 22

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10759690/	moderate [Ki 49 uM]
CYP3A 298	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10759690/	no [Ki >1000 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10759690/	unlikely [Ki 584 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9390115/ \| https://pubmed.ncbi.nlm.nih.gov/10759690/	weak [Ki 38.8 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10759690/	yes [Ki 3.4 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9390115/ \| https://pubmed.ncbi.nlm.nih.gov/10759690/ \| https://pubmed.ncbi.nlm.nih.gov/19845434/ \| https://pubmed.ncbi.nlm.nih.gov/11580286/	yes [Ki 3.7 uM]	yes (co-administration study) Comment: [PMID: 10759690]: Ki = 1.2 uM Sources: https://pubmed.ncbi.nlm.nih.gov/9390115/ \| https://pubmed.ncbi.nlm.nih.gov/10759690/ \| https://pubmed.ncbi.nlm.nih.gov/19845434/ \| https://pubmed.ncbi.nlm.nih.gov/11580286/
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19047469/ \| https://pubmed.ncbi.nlm.nih.gov/14563790/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CYP2J2 56	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CES1 22	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	yes
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	yes
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	yes
OATP2B1 104	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16707409/ \| https://pubmed.ncbi.nlm.nih.gov/28414144/	yes	yes (co-administration study) Comment: Coadministration with Ergoloid mesylates: AUC decreased 30.4% Sources: https://pubmed.ncbi.nlm.nih.gov/16707409/ \| https://pubmed.ncbi.nlm.nih.gov/28414144/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9588	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9588
ChemicalBook	CB7674370	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7674370
MolPort	MolPort-002-507-849	https://www.molport.com/shop/molecule-link/MolPort-002-507-849
ZINC	ZINC000019594599	http://zinc15.docking.org/substances/ZINC000019594599
eMolecules	902580	https://www.emolecules.com/cgi-bin/more?vid=902580

PubMed

Title	Date	PubMed
Drug-induced thrombotic microangiopathy: incidence, prevention and management.	2001	11444722
Indobufen: an updated review of its use in the management of atherothrombosis.	2001	11392445
Current oral antiplatelet agents to prevent atherothrombosis.	2001	11316917
Benefit of ADP receptor antagonists in atherothrombotic patients: new evidence.	2001	11316916
The use of antiplatelet agents in acute cardiac care.	2001 Apr	11450321
Clinical application of procedural platelet monitoring during percutaneous coronary intervention among patients at increased bleeding risk.	2001 Apr	11406730
Aspirin in patients with coronary artery disease: is it simply irresistible?	2001 Apr	11406726
Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: inhibition by sulfaphenazole, omeprazole, and ticlopidine.	2001 Apr	11372587
[Treatment for recurrent paradoxical brain embolism through the patent foramen ovale].	2001 Apr	11360475
Drug-induced cholestasis.	2001 Apr	11352118
CURE--clopidogrel's major advance.	2001 Apr	11351766
[Optimal platelet inhibition therapy in unstable angina pectoris and after coronary interventions].	2001 Apr	11349625
[Pathophysiology of platelet activation and pharmacology of GPIIb/IIIa inhibitors].	2001 Apr	11349624
Regular or "super-aspirins"? A review of thienopyridines or aspirin to prevent stroke.	2001 Apr	11347797
Extracorporeal shockwave lithotripsy in patients treated with antithrombotic agents.	2001 Apr	11339387
[Pressure wire guide provisional coronary stent implantation].	2001 Apr	11337928
Long-term effects of intracoronary beta-radiation in balloon- and stent-injured porcine coronary arteries.	2001 Apr 24	11319203
Oral anticoagulant therapy during and after coronary angioplasty the intensity and duration of anticoagulation are essential to reduce thrombotic complications.	2001 Apr 24	11319192
[Acute heart attacks. Prognosis can be further improved].	2001 Apr 5	11340908
Role of transforming growth factor beta1 in microvascular endothelial cell apoptosis associated with thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome.	2001 Jan	11426486
[Early hepatopathy induced by ticlopidine].	2001 Jan	11387849
Comparison of ticlopidine and cilostazol for the prevention of restenosis after percutaneous transluminal coronary angioplasty.	2001 Jan	11324805
The role of adenosine 5'-diphosphate receptor blockade in patients with cardiovascular disease.	2001 Jul	11448660
Extensive thrombus prior to elective percutaneous coronary intervention.	2001 Jul	11435643
Diffuse alveolar hemorrhage after clopidogrel use.	2001 Jul	11435642
[Toxic skin reaction to clopidogrel].	2001 Jun	11431626
Low-pressure deployment of stents: short- and long-term outcome.	2001 Jun	11428540
Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs.	2001 Jun	11413167
Ticlopidine-induced interstitial pulmonary disease: a case report.	2001 Jun	11399735
Acute and mid-term results of phosphorylcholine-coated stents in primary coronary stenting for acute myocardial infarction.	2001 Jun	11387601
Comparative trial of stent-like balloon angioplasty versus coronary stenting for acute myocardial infarction.	2001 Jun	11387597
Clinical correlates and drug treatment of residents with stroke in long-term care.	2001 Jun	11387503
Ticlopidine monotherapy following coronary stent deployment: "penny wise and pound foolish".	2001 Jun	11385164
Efficacy and safety of ticlopidine monotherapy versus ticlopidine and aspirin after coronary artery stenting: follow-up results of a randomized study.	2001 Jun	11385163
Incidence of thrombotic occlusion and major adverse cardiac events between two and four weeks after coronary stent placement: analysis of 5,678 patients with a four-week ticlopidine regimen.	2001 Jun 15	11419889
Stenting of partial and total coronary occlusions in Trinidad and Tobago.	2001 Mar	11398282
Platelet aggregation inhibition with ticlopidine in the treatment of stroke.	2001 Mar	11355140
[Acute coronary syndromes: an update. I. Pathogenesis and drug therapy].	2001 Mar	11349620
[Acute coronary syndromes: an update. II. Coronary revascularization and risk stratification].	2001 Mar	11349613
[Pharmacy clinics. Medication of the month. Clopidogrel (Plavix)].	2001 Mar	11338792
Thrombotic thrombocytopenic purpura--a syndrome caused by multiple pathogenetic mechanisms.	2001 May	11416985
Cardiovascular drug-drug interactions.	2001 May	11407107
[Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery].	2001 May	11388335
The inhibition of oxygen radical release from human neutrophils by resting platelets is reversed by administration of acetylsalicylic acid or clopidogrel.	2001 May	11378529
Effect of cilostazol on restenosis after coronary angioplasty and stenting in comparison to conventional coronary artery stenting with ticlopidine.	2001 May	11376832
New recommendations from the 1999 American College of Cardiology/American Heart Association acute myocardial infarction guidelines.	2001 May	11346067
Edge stenosis after intracoronary radiotherapy: angiographic, intravascular, and histological findings.	2001 May 1	11331266
Prolonged antiplatelet therapy to prevent late thrombosis after intracoronary gamma-radiation in patients with in-stent restenosis: Washington Radiation for In-Stent Restenosis Trial plus 6 months of clopidogrel (WRIST PLUS).	2001 May 15	11352879
P2y(12), a new platelet ADP receptor, target of clopidogrel.	2001 May 4	11327712
Clopidogrel and aplastic anaemia.	2001 May 5	11360950

Patents

Sample Use Guides

In Vivo Use Guide

250 mg PO q12hr with food

Route of Administration: Oral

In Vitro Use Guide

Following preparation of the platelet concentrate, 1.2 mL of ThromboSol was added to some units (treated units) through a sterile port. We then resuspended the treated PC by gentle massaging and directly placed it at 4°C without shaking. The resulting treated PC contained the following reagents: amiloride (0.25 mM), adenosine (0.1 mM), SNP (50 mkM), dipyridamole (40 mkM) Ticlopidine (0.75 mkM), and quinacrine (0.2 mkM). In parallel, platelet concentrate were stored as control units at 22°C with shaking or at 4°C without shaking. After storage, aliquots of control and treated platelet concentrate were harvested for analysis as follows. The platelet concentrate to be sampled was gently massaged to achieve a homogenous cell suspension, and, by using a syringe with an 18-gauge needle, a 3-mL sample of platelets was removed via the sterile port. We then placed the platelet sample in a 15-mL polypropylene conical tube and centrifuged it at 950 x g for 20 minutes at 22°C to remove the ThromboSol. The resulting platelet pellet was resuspended to the original sample volume with autologous platelet-poor plasma (PPP) and the platelet count was determined with a hematology analyzer

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:00:11 GMT 2023` Edited by `admin` on `Sat Dec 16 05:00:11 GMT 2023`
Record UNII	A1L4914FMF
Record Status	`Validated (UNII)`
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Name

Type

Language

TICLOPIDINE HYDROCHLORIDE

Official Name

English

Ticlopidine hydrochloride [WHO-DD]

Common Name

English

NSC-759165

Code

English

THIENO(3,2-C)PYRIDINE, 5-((2-CHLOROPHENYL)METHYL)-4,5,6,7-TETRAHYDRO-, HYDROCHLORIDE

Systematic Name

English

TICLOPIDINE HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

53-32C

Code

English

TICLID

Brand Name

English

TICLOPIDINE HYDROCHLORIDE [USP-RS]

Common Name

English

IPATON

Brand Name

English

TICLOPIDINE HYDROCHLORIDE [VANDF]

Common Name

English

5-(O-CHLOROBENZYL)-4,5,6,7-TETRAHYDROTHIENO(3,2-C)PYRIDINE HYDROCHLORIDE

Common Name

English

TICLOPIDINE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

TICLOPIDINE HYDROCHLORIDE [MART.]

Common Name

English

TICLOPIDINE HCL

Common Name

English

TICLOPIDINE HYDROCHLORIDE [USAN]

Common Name

English

TICLOPIDINE HYDROCHLORIDE [EP IMPURITY]

Common Name

English

TICLOPIDINE HYDROCHLORIDE [JAN]

Common Name

English

TICLOPIDINE HYDROCHLORIDE [MI]

Common Name

English

TICLOPIDINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C80483