LABELING OF (S)-DES-4-AMINO-3-[I-125]IODOZACOPRIDE (DAIZAC), A HIGH-AFFINITY RADIOLIGAND FOR THE 5-HT-3 RECEPTOR

We have prepared 2-methoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide ([ I-125]DAIZAC, [I-125]-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 (NaI)-I-12 5 and chloramine-T in dilute HCl gave 2.58 +/- 0.22 mCi (52%) of [I-12 5]DAIZAC with >98% radiochemical purity and 1500 Ci/mmol specific acti vity. Saturation analysis of the binding of [I-125]DAIZAC to rat brain homogenates showed a single binding site with a receptor density B-ma x of 0.66 +/- 0.03 pmol/g and a receptor affinity K-D of 0.15 +/- 0.01 nM. Compared to [I-125]iodozacopride, we find the 20-fold higher affi nity and easy preparation of [I-125]DAIZAC to be advantageous for in v itro identification of brain 5-HT-3 receptors.