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
SMILES
ClC1=CC=CC=C1CN2CCC3=C(C2)C=CS3
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
| 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 |
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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: GO:0070527 |
|||
Target ID: CHEMBL2001 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15852221 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Preventing | TICLID Approved UseTiclopidine 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 Date1991 |
|||
| Preventing | TICLID Approved UseTiclopidine 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 Date1991 |
Cmax
| 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 |
T1/2
| 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 |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2% |
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: |
unhealthy, 64.7 |
Other AEs: Leukopenia, Neutropenia... Other AEs: Leukopenia (4 patients) Sources: 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) |
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: |
unhealthy, 70 |
Disc. AE: Agranulocytosis, AST increased... AEs leading to discontinuation/dose reduction: Agranulocytosis (1 patient) Sources: AST increased (1 patient) ALT increased (1 patient) Gamma GT increased (1 patient) ALP increased (1 patient) |
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: |
unhealthy, adult |
Disc. AE: Diarrhea, Nausea... AEs leading to discontinuation/dose reduction: Diarrhea (12.5%) Sources: 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%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Cerebral hemorrhage | 1 patient | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| Gastric ulcer hemorrhage | 1 patient | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| Melena | 1 patient | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| Rash | 1 patient | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| Aspartate aminotransferase increased | 13 patients | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| Neutropenia | 14 patients | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| ALP increased | 2 patients | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| Epistaxis | 2 patients | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| ALT increased | 36 patients | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| Leukopenia | 4 patients | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| Gamma GT increased | 54 patients | 200 mg 1 times / day multiple, oral Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 64.7 |
| ALP increased | 1 patient Disc. AE |
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: |
unhealthy, 70 |
| ALT increased | 1 patient Disc. AE |
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: |
unhealthy, 70 |
| AST increased | 1 patient Disc. AE |
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: |
unhealthy, 70 |
| Agranulocytosis | 1 patient Disc. AE |
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: |
unhealthy, 70 |
| Gamma GT increased | 1 patient Disc. AE |
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: |
unhealthy, 70 |
| Anorexia | 1% Disc. AE |
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: |
unhealthy, adult |
| Dizziness | 1.1% Disc. AE |
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: |
unhealthy, adult |
| Pruritus | 1.3% Disc. AE |
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: |
unhealthy, adult |
| Flatulence | 1.5% Disc. AE |
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: |
unhealthy, adult |
| Vomiting | 1.9% Disc. AE |
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: |
unhealthy, adult |
| Diarrhea | 12.5% Disc. AE |
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: |
unhealthy, adult |
| Purpura | 2.2% Disc. AE |
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: |
unhealthy, adult |
| Neutropenia | 2.4% Disc. AE |
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: |
unhealthy, adult |
| GI pain | 3.7% Disc. AE |
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: |
unhealthy, adult |
| Rash | 5.1% Disc. AE |
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: |
unhealthy, adult |
| Dyspepsia | 7% Disc. AE |
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: |
unhealthy, adult |
| Nausea | 7% Disc. AE |
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: |
unhealthy, adult |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| moderate [Ki 49 uM] | ||||
| no [Ki >1000 uM] | ||||
| unlikely [Ki 584 uM] | ||||
| weak [Ki 38.8 uM] | ||||
| yes [Ki 3.4 uM] | ||||
| yes [Ki 3.7 uM] | yes (co-administration study) Comment: [PMID: 10759690]: Ki = 1.2 uM |
|||
| yes |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | yes (co-administration study) Comment: Coadministration with Ergoloid mesylates: AUC decreased 30.4% |
PubMed
| Title | Date | PubMed |
|---|---|---|
| The role of adenosine 5'-diphosphate receptor blockade in patients with cardiovascular disease. | 2001-07 |
|
| Extensive thrombus prior to elective percutaneous coronary intervention. | 2001-07 |
|
| Diffuse alveolar hemorrhage after clopidogrel use. | 2001-07 |
|
| 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. | 2001-06-15 |
|
| [Toxic skin reaction to clopidogrel]. | 2001-06 |
|
| Low-pressure deployment of stents: short- and long-term outcome. | 2001-06 |
|
| Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs. | 2001-06 |
|
| Ticlopidine-induced interstitial pulmonary disease: a case report. | 2001-06 |
|
| Acute and mid-term results of phosphorylcholine-coated stents in primary coronary stenting for acute myocardial infarction. | 2001-06 |
|
| Comparative trial of stent-like balloon angioplasty versus coronary stenting for acute myocardial infarction. | 2001-06 |
|
| Clinical correlates and drug treatment of residents with stroke in long-term care. | 2001-06 |
|
| Ticlopidine monotherapy following coronary stent deployment: "penny wise and pound foolish". | 2001-06 |
|
| Efficacy and safety of ticlopidine monotherapy versus ticlopidine and aspirin after coronary artery stenting: follow-up results of a randomized study. | 2001-06 |
|
| 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). | 2001-05-15 |
|
| Clopidogrel and aplastic anaemia. | 2001-05-05 |
|
| P2y(12), a new platelet ADP receptor, target of clopidogrel. | 2001-05-04 |
|
| Edge stenosis after intracoronary radiotherapy: angiographic, intravascular, and histological findings. | 2001-05-01 |
|
| Thrombotic thrombocytopenic purpura--a syndrome caused by multiple pathogenetic mechanisms. | 2001-05 |
|
| Cardiovascular drug-drug interactions. | 2001-05 |
|
| [Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery]. | 2001-05 |
|
| The inhibition of oxygen radical release from human neutrophils by resting platelets is reversed by administration of acetylsalicylic acid or clopidogrel. | 2001-05 |
|
| Effect of cilostazol on restenosis after coronary angioplasty and stenting in comparison to conventional coronary artery stenting with ticlopidine. | 2001-05 |
|
| New recommendations from the 1999 American College of Cardiology/American Heart Association acute myocardial infarction guidelines. | 2001-05 |
|
| Long-term effects of intracoronary beta-radiation in balloon- and stent-injured porcine coronary arteries. | 2001-04-24 |
|
| Oral anticoagulant therapy during and after coronary angioplasty the intensity and duration of anticoagulation are essential to reduce thrombotic complications. | 2001-04-24 |
|
| [Acute heart attacks. Prognosis can be further improved]. | 2001-04-05 |
|
| The use of antiplatelet agents in acute cardiac care. | 2001-04 |
|
| Clinical application of procedural platelet monitoring during percutaneous coronary intervention among patients at increased bleeding risk. | 2001-04 |
|
| Aspirin in patients with coronary artery disease: is it simply irresistible? | 2001-04 |
|
| Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: inhibition by sulfaphenazole, omeprazole, and ticlopidine. | 2001-04 |
|
| [Treatment for recurrent paradoxical brain embolism through the patent foramen ovale]. | 2001-04 |
|
| Drug-induced cholestasis. | 2001-04 |
|
| CURE--clopidogrel's major advance. | 2001-04 |
|
| [Optimal platelet inhibition therapy in unstable angina pectoris and after coronary interventions]. | 2001-04 |
|
| [Pathophysiology of platelet activation and pharmacology of GPIIb/IIIa inhibitors]. | 2001-04 |
|
| Regular or "super-aspirins"? A review of thienopyridines or aspirin to prevent stroke. | 2001-04 |
|
| Extracorporeal shockwave lithotripsy in patients treated with antithrombotic agents. | 2001-04 |
|
| [Pressure wire guide provisional coronary stent implantation]. | 2001-04 |
|
| Stenting of partial and total coronary occlusions in Trinidad and Tobago. | 2001-03 |
|
| Platelet aggregation inhibition with ticlopidine in the treatment of stroke. | 2001-03 |
|
| [Acute coronary syndromes: an update. I. Pathogenesis and drug therapy]. | 2001-03 |
|
| [Acute coronary syndromes: an update. II. Coronary revascularization and risk stratification]. | 2001-03 |
|
| [Pharmacy clinics. Medication of the month. Clopidogrel (Plavix)]. | 2001-03 |
|
| Role of transforming growth factor beta1 in microvascular endothelial cell apoptosis associated with thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome. | 2001-01 |
|
| [Early hepatopathy induced by ticlopidine]. | 2001-01 |
|
| Comparison of ticlopidine and cilostazol for the prevention of restenosis after percutaneous transluminal coronary angioplasty. | 2001-01 |
|
| Drug-induced thrombotic microangiopathy: incidence, prevention and management. | 2001 |
|
| Indobufen: an updated review of its use in the management of atherothrombosis. | 2001 |
|
| Current oral antiplatelet agents to prevent atherothrombosis. | 2001 |
|
| Benefit of ADP receptor antagonists in atherothrombotic patients: new evidence. | 2001 |
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8780663
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
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on
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| Record UNII |
OM90ZUW7M1
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Validated (UNII)
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C80483
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METABOLIC ENZYME -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT | |||
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METABOLIC ENZYME -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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IN VITRO
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METABOLITE -> PARENT |
IN VITRO
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ACTIVE MOIETY |