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]ketanse-rin 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-[2-(3-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-propanol)hydrochloride), on α1,-, α2-, β-adrenergic, 5HT,-, 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 5HT,-, α1, α2-, β-adrenergic receptors and muscarinic receptors. Thus, the present study suggests that MCI-9042 is specific for 5HT2-receptor. © 1991, The Pharmaceutical Society of Japan. All rights reserved.