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Abstract

CSH72 (N-methyl-1-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline HCl) inhibited the aggregation and ATP-release reaction induced by platelet-activating factor (PAF) in a concentration-dependent manner in rabbit washed platelets.

The IC50 values of CSH72, kadsurenone and BN52021 on PAF (3·6 nM)-induced platelet aggregation were 61·5 ± 7·2, 18·0 ± 2·8 and 10·6 ± 2·3 μM, respectively. CSH72 also concentration-dependently inhibited [3H]PAF (3·6 nM) binding to washed platelets with an IC50 value of 46·1 ± 1·9 μM. The concentration-response curve of PAF-induced platelet aggregation was shifted to the right by CSH72 with pA2 and pA10 values of 5·47 and 4·68, respectively. CSH72 (300 μM) significantly inhibited PAF (3·6 nM)-induced thromboxane B2 formation but exhibited no effects on those induced by arachidonic acid (100 μM) and thrombin (0·1 units mL−1). CSH72 (300 μM) also completely abolished [3H]inositol monophosphate formation induced by PAF but not that caused by collagen or thrombin in the presence of indomethacin (20 μM).

It is suggested that CSH72 is a specific PAF-receptor antagonist as an antiplatelet aggregatory agent.