Synthesis of radioiodinated analogs of 2-(4-phenylpiperidino)cyclohexanol (vesamicol) as vesamicol-like agent.
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.
Shiba
K
K
Radioisotope Center, School of Medicine, Kanazawa University, Japan.
Mori
H
H
Matsuda
H
H
Tsuji
S
S
Kuji
I
I
Sumiya
H
H
Kinuya
K
K
Tonami
N
N
Hisada
K
K
Sumiyosi
T
T
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism*; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013329:Structure-Activity Relationship
D007457:Iodine Radioisotopes; D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; D011950:Receptors, Cholinergic; C083232:vesamicol receptor; C006189:vesamicol