Shiba K, Mori H, Matsuda H, Tsuji S, Kuji I, Sumiya H, Kinuya K, Tonami N, Hisada K, Sumiyosi T
Radioisotope Center, School of Medicine, Kanazawa University, Japan.
Nucl Med Biol. 1995 Feb;22(2):205-10. doi: 10.1016/0969-8051(94)00093-y.
Three iodovesamicol analogs, iodinated at the ortho, meta, and para positions of the 4-phenylpiperidine moiety, were synthesized and labeled with 125I by isotopic exchange reaction. Their potencies as a vesamicol-like drug were evaluated with competitive inhibition studies using (-)[3H]vesamicol. The radiochemical yields were 40-85%, the radiochemical purities exceeded 95% and their specific activities were 370-740 GBq/mmol. The descending order of binding affinity of the tested compounds against the vesamicol receptor was m-iodovesamicol > o-iodovesamicol > p-iodovesamicol. The receptor binding affinity of m-iodovesamicol (IC50 = 133 nM) was comparable with that of vesamicol (IC50 = 109 nM). Therefore, the meta position of the 4-phenylpiperidinyl fragment of vesamicol was the optimum site for iodination, and radioiodinated m-iodovesamicol may serve as a useful radiopharmaceutical for in vitro and in vivo studies of presynaptic cholinergic neurons in rats.
