The basic pharmacology of ticlopidine and clopidogrel.
Ticlopidine and clopidogrel are two thienopyridines with potent and apparently irreversible platelet inhibitory properties. The antiplatelet effects are mainly directed against ADP-induced stimulation of platelet function, in particular ADP-induced inhibition of adenylyl cyclase stimulation. There is evidence for additional effects, including inhibition of agonist-induced intracellular Ca(++) mobilization, interference with GpIIb/IIIa receptor/agonist interaction and inhibition of α-granule secretion. However, these actions are probably secondary to the ADP-antagonistic action. Thienopyridines do not directly interfere with arachidonic acid metabolism. The substances are inactive in vitro and have to undergo some form of bioactivation in vivo which requires 3 to 5 days of treatment for a maximum effect. The nature of the postulated active metabolite(s) is still unknown. From a pharmacological point of view, thienopyridines may be considered interesting alternatives to acetylsalicylic acid with particular value in shear-stress-mediated platelet activation, for example in prevention of acute thrombembolic risk in injury-related vessel stenosis.
Institut für Pharmakologie, Heinrich-Heine-Universität Dusseldorf, Moorenstr 5, D-40225, Düsseldorf, Germany, Tel: (211) 311-2500, Fax: (211) 311-4781.
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