title: Effects of sarpogrelate, a novel 5-HT2 antagonist, on 5-HT-induced endothelium-dependent relaxations in porcine coronary artery.
abstract: 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 x 10(-6) M) and precontracted by U 46619 (5 x 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.
authors.affiliation: Department of Pharmacology, Niigata College of Pharmacy, Japan.
authors.forename: Mamunur
authors.initials: M
authors.lastname: Rashid
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nagatomo
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate; D012701:Serotonin