Synthesis of radioiodinated analogs of 2-(4-Phenylpiperidino)cyclohexanol (vesamicol) as vesamicol-like agent

• Published in: Nuclear medicine and biology 1995-02, Vol.22 (2), p.205-210
• Main Authors: Shiba, K., Mori, H., Matsuda, H., Tsuji, S., Kuji, I., Sumiya, H., Kinuya, K., Tonami, N., Hisada, K., Sumiyosi, T.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Membrane - metabolism; Cerebral Cortex - metabolism; Contrast media. Radiopharmaceuticals; Iodine Radioisotopes; Isotope Labeling - methods; Kinetics; Male; Medical sciences; Neuromuscular Depolarizing Agents - metabolism; Pharmacology. Drug treatments; Piperidines - metabolism; Radioligand Assay - methods; Rats; Rats, Sprague-Dawley; Receptors, Cholinergic - metabolism; Structure-Activity Relationship
• ISSN: 0969-8051; 1872-9614
• 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 (IC 50 = 133 nM) was comparable with that of vesamicol (IC 50 = 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.