Levamisole inhibits in vivo rat platelet aggregation by a release of prostacyclin-like factor.
1. The anti-thrombotic effect of levamisole (LMS) and acetylsalicylic acid (ASA) were examined in vitro and in vivo models. 2. LMS inhibits rat platelet aggregation induced by either adenosine 5'-diphosphate (ADP) or collagen (CLG) in vitro and in vivo. 3. LMS is more active in vivo than in vitro while acetylsalicylic acid (ASA) is more active in vitro than in vivo. It seems that in vivo LMS does not act by blocking thromboxane A2 formation only, but via participation of an endogenous factor. 4. The release of LMS-induced anti-thrombotic factor is inhibited by ASA pretreatment, indicating to be a cyclooxygenase metabolite of arachidonic acid. 5. The LMS-induced anti-thrombotic factor has a t1/2 of 3.6 +/- 0.8 min that is similar to the t1/2 of synthetic prostacyclin (PGI2) tested in our system (3.9 +/- 0.5 min; P = NS). 6. The release of PGI2-like substance from vascular tissue is LMS dose-dependent.
Pinto
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A
Department of Experimental Pharmacology, Naples, Italy.
Sorrentino
R
R
Sorrentino
L
L
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism*; D006207:Half-Life; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects; D007978:Levamisole / Q000494:pharmacology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000494:pharmacology
D001095:Arachidonic Acids; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D007978:Levamisole; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D011464:Epoprostenol; D001241:Aspirin