title: Synthesis and evaluation of radiolabeled piperazine derivatives of vesamicol as SPECT agents for cholinergic neurons.
abstract: To diagnose and investigate neurodegenerative diseases affecting cholinergic neuron density, piperazine derivatives of vesamicol were synthesized and evaluated. Previously, we reported that trans-5-iodo-2-hydroxy-3-[4-phenylpiperazinyl] tetralin (DRC140, 1) possessed high selectivity for vesicular acetylcholine transporter (VAChT). In present study of the effect of alkyl substituents, we observed that the introduction of a methyl group into the ortho or meta positions of the phenyl group of 1 increased affinity for VAChT. trans-5-Iodo-2-hydroxy-3-[4-[2-methylphenyl] piperazinyl]tetralin (2) displayed high affinity and specificity for VAChT. The regional distributions of radioactivity in the rat brain correlated well with known patterns of central cholinergic innervation. [(123)I]2 is a potentially useful compound for SPECT imaging.
authors.affiliation: Research Center, Daiichi Radioisotope Laboratories, LTD., 453-1, Shimo-Okura, Matsuo-Machi, Sanbu-Gun, 289-1592, Chiba, Japan. bkazunori@drl.co.jp
authors.forename: K
authors.initials: K
authors.lastname: Bando
authors.forename: K
authors.initials: K
authors.lastname: Taguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Ginoza
authors.forename: T
authors.initials: T
authors.lastname: Naganuma
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: K
authors.initials: K
authors.lastname: Takatoku
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D009474:Neurons / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; D019275:Radiopharmaceuticals; C006189:vesamicol