Labeling of ( <i>S</i> )‐DES‐4‐amino‐3‐[ ¹²⁵ I]iodozacopride (DAIZAC), a high‐affinity radioligand for the 5‐HT‐3 receptor

Abstract

We have prepared (S)-5-chloro-3-[125I]iodo-2-methoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)-benzamide ([125I]DAIZAC, [125I]-3) as a radioligand for characterization of the 5-HT-3 receptor. Preparation of the 3-tri-n-butylstannyl precursor was accomplished from the corresponding unlabeled DAIZAC by reaction with bis(tributyltin). Treatment of the precursor with 5 mCi of Na125I and chloramine-T in dilute HCl gave 2.58 ± 0.22 mCi (52%) of [125I]DAIZAC with >98% radiochemical purity and 1500 Ci/mmol specific activity. Saturation analysis of the binding of [125I]DAIZAC to rat brain homogenates showed a single binding site with a receptor density Bmax of 0.66 ± 0.03 pmol/g and a receptor affinity KD of 0.15 ± 0.01 nM. Compared to [125I]iodozacopride, we find the 20-fold higher affinity and easy preparation of [125I]DAIZAC to be advantageous for in vitro identification of brain 5-HT-3 receptors.