Anti-thrombotic and anti-inflammatory activities of protopine

The effects of protopine on human platelet aggregation and arachidonic acid (AA) metabolism via cyclooxygenase (COX) and lipoxygenase (LOP) enzymes were examined. Platelet aggregation induced by various platelet agonists (AA, ADP, collagen and PAF) was strongly inhibited by protopine in a concentration-related manner. The IC50 values (mu M) of protopine (mean +/- SEM) against: AA; 12 +/- 2: ADP; 9 +/- 2: collagen, 16 +/- 2 and PAF; 11 +/- 1, were much less than those observed for aspirin. In addition, protopine selectively inhibited the synthesis of thromboxane A(2) (TXA(2)) via COX pathway and had no effect on the LOP pathway in platelets. In vivo, pretreatment with protopine (50-100 mg kg(-1)) protected rabbits from the lethal effects of AA (2 mg kg(-1)) or PAF (11 mu g kg(-1)) in a dose-dependent fashion. Protopine (50-100 mg kg(-1)) also inhibited carrageenan-induced-rat paw oedema with a potency of three-fold as compared to aspirin. These results are suggestive that protopine acts as a potent inhibitor of thromboxane synthesis and PAF with anti-inflammatory properties. (C) 1997 The Italian Pharmacological Society.