TICLOPIDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H14ClNS
Molecular Weight	263.786
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=PHWBOXQYWZNQIN-UHFFFAOYSA-N

InChI=1S/C14H14ClNS/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

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

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 75 Target ID: GO:0070527 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/19-979S018_Ticlid_prntlbl.pdf	Inhibitor 8228
Purinergic receptor P2Y12 23 Target ID: CHEMBL2001 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15852221	Antagonist 2760

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 8360	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 6.8886718E11
Coronary artery disease 48 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/19-979S018_Ticlid_prntlbl.pdf	Preventing		Approved 8360	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 6.8886718E11

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 1709	inhibitor 1752 substrate 1010	inhibitor 1837 substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1463 CYP1A2 1509 CYP2E1 876 CYP3A 211 CYP2B6 799	OATP2B1 103 CYP1A2 1032 CYP2A6 523 CYP2B6 660 CYP2C8 688 CYP2C19 985 CYP3A5 391 CYP2J2 56 CES1 22

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1673	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/10759690/	moderate [Ki 49 uM]
CYP3A 295	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/10759690/	no [Ki >1000 uM]
CYP2E1 964	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/10759690/	unlikely [Ki 584 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/9390115/ \| https://pubmed.ncbi.nlm.nih.gov/10759690/	weak [Ki 38.8 uM]
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/10759690/	yes [Ki 3.4 uM]
CYP2C19 1537	inhibitor 3240 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 985	inhibitor 3240 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 523	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CYP2C8 688	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CYP2J2 56	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CYP3A5 391	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	no
CES1 22	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	yes
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	yes
CYP2B6 660	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	yes
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	yes
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24170778/	yes
OATP2B1 103	substrate 3326 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
Novel platelet inhibitors.	2001	11160773
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
Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: inhibition by sulfaphenazole, omeprazole, and ticlopidine.	2001 Apr	11372587
[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
Extracorporeal shockwave lithotripsy in patients treated with antithrombotic agents.	2001 Apr	11339387
[Pressure wire guide provisional coronary stent implantation].	2001 Apr	11337928
Clinical and angiographical follow-up after implantation of a 6--12 microCi radioactive stent in patients with coronary artery disease.	2001 Apr	11286524
Results of CURE trial for acute coronary syndrome.	2001 Apr 11	11308379
Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials.	2001 Apr 17	11306525
Newer antiplatelet therapies in stroke prevention.	2001 Feb	11280112
[Late stent thrombosis after intracoronary brachytherapy. A case report and review of the literature].	2001 Feb	11263004
Protective effects of SM-20302, an orally active GPIIb/IIIa antagonist, in an ADP/epinephrine-induced guinea pig model of transient cerebral ischemia.	2001 Feb 1	11228335
Comparison of effects of clopidogrel versus ticlopidine on platelet function in patients undergoing coronary stent placement.	2001 Feb 1	11165971
Fatal aplastic anaemia associated with clopidogrel.	2001 Feb 10	11273071
Combination therapy with aspirin plus clopidogrel versus aspirin plus ticlopidine for prevention of subacute thrombosis after successful native coronary stenting.	2001 Feb 15	11179539
Sustained benefit over four years from an initial combined antiplatelet regimen after coronary stent placement in the ISAR trial. Intracoronary Stenting and Antithrombotic Regimen.	2001 Feb 15	11179521
[Update on the treatment with platelet antiaggregation agents].	2001 Jan	11291339
[The new limitations of the Italian Regulatory Agency on Drugs].	2001 Jan	11216082
Stasis ulcers refractory to therapy--accelerated healing by treatment with clopidogrel +/- dalteparin: a preliminary report.	2001 Jan	11190899
Fixed drug eruption from ticlopidine, with positive lesional patch test.	2001 Jan	11156015
Angioplasty increases coronary sinus F2-isoprostane formation: evidence for in vivo oxidative stress during PTCA.	2001 Jan	11153776
[Leukocytoclastic vasculitis associated with ticlopidine].	2001 Jan	11141463
Antithrombotic therapy in cardiac stent patients.	2001 Jan	11139803
Diabetes mellitus with left transverse sinus thrombosis and right transverse sinus aplasia.	2001 Jan	11137180
Effects of cilostazol on late lumen loss and repeat revascularization after Palmaz-Schatz coronary stent implantation.	2001 Jan	11136497
Active-control trials: how would a new agent compare with placebo? A method illustrated with clopidogrel, aspirin, and placebo.	2001 Jan	11136483
Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement.	2001 Jan	11119474
[2 platelet inhibitors administered at the same time. Improved prognosis in myocardial infarct?]].	2001 Jan 11	11219401
Local delivery of enoxaparin to decrease restenosis after stenting: results of initial multicenter trial: Polish-American Local Lovenox NIR Assessment study (The POLONIA study).	2001 Jan 2	11136681
Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery.	2001 Jan 23	11157686
Localized intracoronary gamma-radiation therapy to inhibit the recurrence of restenosis after stenting.	2001 Jan 25	11172151
[Cholestatic hepatitis by ticlopidin].	2001 Jan 27	11181293
Febrile pancytopenia associated with clopidogrel.	2001 Jan 8	11146710
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
Efficacy and safety of ticlopidine monotherapy versus ticlopidine and aspirin after coronary artery stenting: follow-up results of a randomized study.	2001 Jun	11385163
Platelet aggregation inhibition with ticlopidine in the treatment of stroke.	2001 Mar	11355140
[Pharmacy clinics. Medication of the month. Clopidogrel (Plavix)].	2001 Mar	11338792
Pharmacokinetic differences between lansoprazole enantiomers and contribution of cytochrome P450 isoforms to enantioselective metabolism of lansoprazole in dogs.	2001 Mar	11256484
Metabolic characterization of the major human small intestinal cytochrome p450s.	2001 Mar	11181505
[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
Edge stenosis after intracoronary radiotherapy: angiographic, intravascular, and histological findings.	2001 May 1	11331266
P2y(12), a new platelet ADP receptor, target of clopidogrel.	2001 May 4	11327712

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 `Wed Jul 05 23:12:59 UTC 2023` Edited by `admin` on `Wed Jul 05 23:12:59 UTC 2023`
Record UNII	OM90ZUW7M1
Record Status	`Validated (UNII)`
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Name

Type

Language

TICLOPIDINE

Official Name

English

TICLOPIDINE [MI]

Common Name

English

Ticlopidine [WHO-DD]

Common Name

English

TICLOPIDINE [VANDF]

Common Name

English

ticlopidine [INN]

Common Name

English

TICLOPIDIN-PUREN

Brand Name

English

Classification Tree Code System Code

NDF-RT

N0000175578