MCI-9042 : High Affinity for Serotonergic Receptors as Assessed by Radioligand Binding Assay

Abstract

This study assessed the specificity of displacement potencies of MCI-9042 ((±)-1-[o-[2-(m-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-propyl hydrogen succinate hydrochloride), a new antiplatelet agent, in [³H]4-bromo-2, 5-dimethoxyphenylisopropylamine ([³H]DOB) and [³H] ketanserin binding to 5HT₂-serotonergic receptors in the rat brain using the radioligand binding method. The assessment of the displacement potencies of MCI-9042 and its derivative, M-1 (((±)-1-[2-(3-methoxyphenyl) ethyl] phenoxy]-3-(dimethylamino)-2-propanol)hydrochloride), on α₁-, α₂-, β-adrenergic, 5HT₁-, 5HT₂- and muscarinic receptors were also studied. MCI-9042 and M-1 showed strong displacement effects to 5HT₂-receptors using [³H] DOB binding and [³H] ketanserin binding sites, and weak displacement effects for [³H] serotonin, [³H] prazosin, [³H] p-aminoclonidine, [³H] CGP12177 and [³H] QNB binding to 5HT₁-, α₁-, α₂-, β-adrenergic receptors and muscarinic receptors. Thus, the present study suggests that MCI-9042 is specific for 5HT₂-receptor.