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Titolo:
THROMBOLYTIC ACTION OF TICLOPIDINE - POSSIBLE MECHANISMS
Autore:
GRYGLEWSKI RJ; KORBUT R; SWIES J; KOSTKATRABKA E; BIERON K; ROBAK J;
Indirizzi:
JAGIELLONIAN UNIV,COLL MED,DEPT PHARMACOL,16 GRZEGORZECKA PL-31531 KRAKOW POLAND
Titolo Testata:
European journal of pharmacology
fascicolo: 1, volume: 308, anno: 1996,
pagine: 61 - 67
SICI:
0014-2999(1996)308:1<61:TAOT-P>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLATELET ADENYLATE-CYCLASE; FIBRINOLYTIC SYSTEM; RELAXING FACTOR; NITRIC-OXIDE; PROSTACYCLIN; CLOPIDOGREL; ADP; ENDOTHELIUM; BINDING; DISEASE;
Keywords:
TICLOPIDINE; THROMBOLYSIS; ANTIPLATETLET POTENCY; PROSTACYCLIN; NITRIC OXIDE (NO); TISSUE PLASMINOGEN ACTIVATOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
R.J. Gryglewski et al., "THROMBOLYTIC ACTION OF TICLOPIDINE - POSSIBLE MECHANISMS", European journal of pharmacology, 308(1), 1996, pp. 61-67

Abstract

Ticlopidine (Ticlide), an anti-platelet drug with a broad scope of clinical applications, is claimed to be an antagonist of adenosine diphosphate on platelet receptors. In vitro this antagonism cannot be demonstrated. Ex vivo it is detectable many hours after oral administrationof the drug, perhaps subsequently to its biotransformation to an unknown metabolite. Here, we report for the first time that in patients with peripheral arterial disease and in cats with extracorporal circulation ticlopidine evokes instantaneous thrombolytic or fibrinolytic effects which are not associated with inhibition of platelet aggregation. Shortening of euglobulin clot lysis time and increase in plasma levelsof tissue plasminogen activator were observed 1-2 h after oral ingestion of ticlopidine at a single dose of 500 mg. In cats ticlopidine produced instantaneous anti-thrombotic and thrombolytic effects at doses of 0.3-1 mg/kg and 10-15 mg/kg i.v., respectively. Thrombolysis by ticlopidine (10 mg/kg i.v.) was comparable to that by prostacyclin at a dose of 0.3 mu g/kg i.v. Ticlopidine at a concentration of 100 mu M increased endothelial thromboresistance in vitro. The drug did not inhibit the activity of cyclooxygenase-1 or 12-lipoxygenase while it inhibited lipid autooxidation (IC50 = 18 mu M) in rat liver microsomes. Our data point to a possibility that the therapeutic efficacy of ticlopidine might be associated not only with its delayed anti-platelet effects but also with its immediate thrombolytic action which is likely to be mediated by endothelial prostacyclin and tissue plasminogen activator rather than by platelet mechanisms.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 00:03:10