Binding Affinity 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), in the Rabbit Platelet Membrane

Abstract

The object of this study was to investigate the binding affinity of a newly synthesized 5-HT₂ antagonist, (N-[2-[4-(5H-dibenzo[a, d]cyclohepten-5-ylidene)-piperidino]ethyl]-1-formyl-4-piperidinecarboxamide monohydrochloride monohydrate) (AT-1015), in the rabbit platelet membrane using [³H]-ketanserin by radioligand binding assay method and to compare the results with other selective 5-HT₂ antagonists. The results showed that AT-1015 displayed high affinity to 5-HT₂ receptors in rabbit platelet membranes. The pK_i value of AT-1015 was 7.40, which is slightly lower than that of ketanserin, but higher than that of cyproheptadine. On the other hand, the displacement potency of AT-1015 for 5-HT₂ receptors in rabbit platelets was similar to those of sarpogrelate and ritanserin. This is the first report of the high affinity of AT-1015 in rabbit platelets.