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Titolo:
Thrombolysis by thienopyridines and their congeners
Autore:
Gryglewski, RJ; Dupin, JP; Uracz, W; Swies, J; Madej, J; Hou, G; Gravier, D; Casadebaig, F;
Indirizzi:
Jagiellonian Univ, Chair Pharmacol, Coll Med, PL-31531 Krakow, Poland Jagiellonian Univ Krakow Poland PL-31531 ll Med, PL-31531 Krakow, Poland Univ Bordeaux 2, Chair Pharmaceut Organ Chem, Bordeaux, France Univ Bordeaux 2 Bordeaux France Pharmaceut Organ Chem, Bordeaux, France
Titolo Testata:
JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
fascicolo: 4, volume: 51, anno: 2000,
parte:, 1
pagine: 683 - 693
SICI:
0867-5910(200012)51:4<683:TBTATC>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
AORTIC ENDOTHELIAL-CELLS; PLATELET-AGGREGATION; RELAXING FACTOR; IN-VITRO; TICLOPIDINE; CLOPIDOGREL; ASPIRIN; PROSTACYCLIN; COMBINATION; DERIVATIVES;
Keywords:
ticlopidine; clopidogrel; thienopyridine and pyridopyrimidine derivatives; vascular endothelium; prostacyclin; tissue plasminogen activator; thrombolysis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Gryglewski, RJ Jagiellonian Univ, Chair Pharmacol, Coll Med, Grzegorzecka 16, PL-31531 Krakow, Poland Jagiellonian Univ Grzegorzecka 16 Krakow Poland PL-31531 d
Citazione:
R.J. Gryglewski et al., "Thrombolysis by thienopyridines and their congeners", J PHYSL PH, 51(4), 2000, pp. 683-693

Abstract

We propose that anti-platelet thienopyridines, such as ticlopidine or clopidogrel, are thrombolytic owing to endothelial release of prostacyclin (PGI) and tissue plasminogen activator (t-PA). In this study we used anaesthetised Wistar rats with extracorporal circulation in which arterial blood superfused thrombi which adhered to a strip of collagen. Weight of thrombi was continuously monitored. When administered intravenously, clopidogrel or itsR enantiomer deprived of anti-platelet action, both at doses of 3 mg kg(-1) produced lost in weight of thrombi by 14.1 +/- 1.3% or 16.0 +/- 1.4% (n =9), and at doses 10 mg kg(-1) by 28.3 +/- 2.3% or 30.4 +/- 1.9% (n = 8), respectively. Maximum of thrombolysis occurred 30-45 min following the drug administration. Ticlopidine at a dose of 30 mg kg(-1) reduced weight of thrombi by 33.7 +/- 1.7% (n = 32). Thrombolytic action of ticlopidine was accompanied by a rise in 6 keto-PGF(1 alpha) blood levels from 0.42 +/- 0.10 to1.58 +/- 0.29 ng ml(-1) and t-PA antigen plasma levels from 4.70 +/- 1.00 to 12.90 +/- 1.15 ng ml(-1) (n = 7). Five out of eleven tested thienopyridine congeners with pyrimidine or pyrimidinone instead of pyridine rings had thrombolytic potencies similar to that of clopidogrel (ED(50)s at a range of 6.2-11.4 mg kg(-1)). A substantial increase in thrombolytic potency (ED(50)s at a range of 0.3-2.1 mg kg(-1)) was observed for congeners in which thienyl ring was condensed with an additional cyclopentyl, cyclohexyl or cycloheptyl structures or in which thienopyridine complex was replaced for a pyridopyrimidine one. We claim that thienopyridines, independently of their delayed anti-platelet action, do produce immediate thromboiysis in vivo. This new activity emulates capacity of their native, non-metabolised moleculesto release prostacyclin and tissue plasminogen activator. We have also shown that structural changes in molecules of thienopyridines may intensify their thrombolytic potency.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 01:02:37