MCI-9042 - HIGH-AFFINITY FOR SEROTONERGIC RECEPTORS AS ASSESSED BY RADIOLIGAND BINDING ASSAY

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 [H-3]4-bromo-2,5-dimethoxyphenylispropylamine ([H-3]DOB) and [H-3]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-[2-(3-methoxyphenyl)ethyl)phenoxy]-3-(dimethylamino)-2-propanol)hydrochloride), on alpha-1-, alpha-2-, beta-adrenergic, 5HT1-, 5HT2- and muscarinic receptors were also studied. MCI-9042 and M-1 showed strong displacement effects to 5HT2-receptors using [H-3]DOB binding and [H-3]ketanserin binding sites, and weak displacement effects for [H-3]serotonin, [H-3]prazosin, [H-3]p-aminoclonidine, [H-3]CGP12177 and [H-3]QNB binding to 5HT1-, alpha-1-, alpha-2-, beta-adrenergic receptors and muscarinic receptors. Thus, the present study suggests that MCI-9042 is specific for 5HT2-receptor.