Assessment of Affinity and Dissociation Ability of a Newly Synthesized 5-HT2 Antagonist, AT-1015: Comparison With Other 5-HT2 Antagonists.

DOI Web Site Web Site Web Site PubMed 被引用文献5件 参考文献39件

この論文をさがす

抄録

This study investigated the binding affinities of a newly synthesized 5-HT2 antagonist, AT-1015 (N-[2-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-piperidino]ethyl]-1-formyl-4-piperidinecarboxamide monohydrochloride monohydrate) for [3H]ketanserin bindings to 5-HT2 receptors in the rabbit cerebral cortex membranes using the radioligand binding assay method. The affinity of this compound was also compared with other 5-HT2-selective antagonists such as ketanserin, sarpogrelate, cyproheptadine and ritanserin, and the results showed that AT-1015 has a high pKi value for the 5-HT2 receptor. The rank order of these antagonists are: ritanserin > ketanserin ≅ AT-1015 > cyproheptadine ≅ sarpogrelate. We also evaluated the dissociation ability (slow or rapid) of AT-1015 in the rabbit cerebral cortex membrane and compared it with other 5-HT2 antagonists using the radioligand binding assay method. The blockade of [3H]ketanserin binding sites in the rabbit cerebral cortex induced by ketanserin and sarpogrelate was readily reversed by washing, whereas the inhibition by AT-1015, cyproheptadine and ritanserin was not readily reversed by washing. The % of control after washing are 76.10% and 49.55% for AT-1015 at 10−7.5 and 10−7.0 M, 67.32% and 50.17% for cyproheptadine at 10−7.5 and 10−7.0 M, and 72.38% and 39.80% for ritanserin at 10−9.5 and 10−9.0 M concentrations, respectively. Thus, these findings suggest that AT-1015 has antagonistic properties towards the 5-HT2 receptor and also shows that AT-1015 slowly dissociates from the 5-HT2 receptor, whereas, ketanserin and sarpogrelate dissociate rapidly from the 5-HT2 receptor, which do not correlate with their affinity.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 87 (3), 189-194, 2001

    公益社団法人 日本薬理学会

被引用文献 (5)*注記

もっと見る

参考文献 (39)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ