title: Syntheses and in vitro evaluation of decalinvesamicol analogues as potential imaging probes for vesicular acetylcholine transporter (VAChT).
abstract: A series of vesamicol analogues, o-iodo-trans-decalinvesamicol (OIDV) or o-bromo-trans-decalinvesamicol (OBDV), were synthesized and their affinities to vesicular acetylcholine transporter (VAChT) and σ receptors (σ-1, σ-2) were evaluated by in vitro binding assays using rat cerebral or liver membranes. OIDV and OBDV showed greater binding affinity to VAChT (K(i) = 20.5 ± 5.6 and 13.8 ± 1.2 nM, respectively) than did vesamicol (K(i) = 33.9 ± 18.1 nM) with low affinity to σ receptors. A saturation binding assay in rat cerebral membranes revealed that [(125)I]OIDV had a single high affinity binding site with a K(d) value of 1.73 nM and a B(max) value of 164.4 fmol/mg protein. [(125)I]OIDV revealed little competition with inhibitors, which possessed specific affinity to each σ (σ-1 and σ-2), serotonin (5-HT(1A) and 5-HT(2A)), noradrenaline, and muscarinic acetylcholine receptors. In addition, BBB penetration of [(125)I]OIDV was verified in in vivo. The results of the binding studies indicated that OIDV and OBDV had great potential to be VAChT imaging probes with high affinity and selectivity.
authors: Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan. t-kozaka@staff.kanazawa-u.ac.jp
authors: Takashi
authors: T
authors: Kozaka
authors: Izumi
authors: I
authors: Uno
authors: Yoji
authors: Y
authors: Kitamura
authors: Daisuke
authors: D
authors: Miwa
authors: Kazuma
authors: K
authors: Ogawa
authors: Kazuhiro
authors: K
authors: Shiba
mesh_terms: D000818:Animals; D008297:Male; D015394:Molecular Structure; D010880:Piperidines / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000032:analysis* / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000032:analysis / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000032:analysis* / Q000378:metabolism
chemical_list: D010880:Piperidines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; C578221:o-iodo-trans-decalinvesamicol