抄録
The aim of the present study was to examine the effects of sarpogrelate, a 5-HT2 antagonist, on 5-HT-induced endothelium-dependent relaxation in isolated porcine coronary artery preincubated with ketanserin (3 × 10−6 M) and precontracted by U 46619 (5 × 10−9 M) and compare its effects with other 5-HT2 antagonists such as ritanserin and cyproheptadine. The investigation showed that sarpogrelate (10−7 – 10−5 M) had a weak antagonistic effect on 5-HT-induced relaxation and its effect was weaker than that of ritanserin (10−9 – 10−7 M) and cyproheptadine (10−8 – 10−6 M). The rank order of the antagonistic effects was: ritanserin > cyproheptadine > sarpogrelate. The study also showed that both sarpogrelate and ritanserin had no inhibitory effect on bradykinin-induced relaxation. In our previous study, we investigated the binding affinity of sarpogrelate, ritanserin and cyproheptadine to the 5-HT2A-receptor in rabbit cerebral cortex membranes and the pKi values found were 7.22, 8.98 and 7.54, respectively (M. Rashid et al., Jpn J Pharmacol 87, 189 – 194, 2001). Rank order of the calculated ratio of concentration of pA2 or pD′2 vs Ki was: sarpogrelate > ritanserin > cyproheptadine. Thus, these findings suggest that sarpogrelate has the lowest antagonistic effect on 5-HT-induced endothelium-dependent relaxation and the highest selectivity towards 5-HT2A receptor and might also be the safest drug with respect to its clinical implications in comparison with ritanserin and cyproheptadine.
