Synthesis and evaluation of radiolabeled piperazine derivatives of vesamicol as SPECT agents for cholinergic neurons.
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.
Bando
K
K
Research Center, Daiichi Radioisotope Laboratories, LTD., 453-1, Shimo-Okura, Matsuo-Machi, Sanbu-Gun, 289-1592, Chiba, Japan. bkazunori@drl.co.jp
Taguchi
K
K
Ginoza
Y
Y
Naganuma
T
T
Tanaka
Y
Y
Koike
K
K
Takatoku
K
K
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
D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; D019275:Radiopharmaceuticals; C006189:vesamicol