ANTITHROMBOTIC AND ANTIINFLAMMATORY 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 platele t agonists (AA, ADP, collagen and PAF) was strongly inhibited by proto pine in a concentration-related manner. The IC50 values (mu M) of prot opine (mean +/- SEM) against: AA; 12 +/- 2: ADP; 9 +/- 2: collagen, 16 +/- 2 and PAF; 11 +/- 1, were much less than those observed for aspir in. In addition, protopine selectively inhibited the synthesis of thro mboxane A(2) (TXA(2)) via COX pathway and had no effect on the LOP pat hway 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 pote ncy of three-fold as compared to aspirin. These results are suggestive that protopine acts as a potent inhibitor of thromboxane synthesis an d PAF with anti-inflammatory properties. (C) 1997 The Italian Pharmaco logical Society.