Synthesis and 5-HT-3 receptor binding activity of 5-[125I]iodo-2,3-dimethoxy-N-(1-azabicyclo[2.2.2]oct-3-yl]benzamide and its 5-halogen-2-alkoxyl homologues

Article abstract of DOI:10.1016/S0223-5234(97)81676-5

(S)-5-Iodo-2,3-dimethoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide (MIZAC) was prepared from 5-iodo-2,3-dimethoxybenzoyl chloride and (S)-3-aminoquinuclidine. [¹²⁵I]Iodode-stannylation of its corresponding 5-tri-n-butyltin derivative gave [¹²⁵I]-MIZAC at 1800 Ci/mmol. Binding of [¹²⁵I]-MIZAC in rat entorhinal cortex revealed a K(D) of 1.37 ± 0.21 nM. A series of racemic 2-O-alkyl derivatives of MIZAC were prepared and 5-HT-3 receptor affinities were determined by inhibition of [¹²⁵I]-MIZAC binding. Optimal affinity for the receptor was obtained with small, electron-withdrawing substituents in the aromatic 5-position and with bulky substituents in the 3-position. [¹²⁵I]-MIZAC is a selective radioligand useful for in vitro identification of the 5-HT-3 receptor.