CSH72—A Specific Antagonist of Platelet-activating Factor in Rabbit Platelets
Article first published online: 11 MAR 2011
1995 Royal Pharmaceutical Society of Great Britain
Pharmacy and Pharmacology Communications
Volume 1, Issue 11, pages 525–529, November 1995
How to Cite
GUH, J.-H., KO, F.-N., LEE, C.-S. and TENG, C.-M. (1995), CSH72—A Specific Antagonist of Platelet-activating Factor in Rabbit Platelets. Pharmacy and Pharmacology Communications, 1: 525–529. doi: 10.1111/j.2042-7158.1995.tb00371.x
- Issue published online: 11 MAR 2011
- Article first published online: 11 MAR 2011
- November 3, 1995, November 20, 1995
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.