title: Synthesis and evaluation of 2-amino-dihydrotetrabenzine derivatives as probes for imaging vesicular monoamine transporter-2.
abstract: A novel series of analogs of 2-amino-dihydrotetrabenazine derivatives, 4-6, targeting the vesicular monoamine transporter have been prepared. In vitro binding was carried out in tissue homogenates prepared from rat striatal tissue homogenates with both [(125)I]-iodovinyl-TBZ and [(3)H]DTBZ. There was a good correlation (r(2)=0.925) between the affinities of the different compounds for [(125)I]-iodovinyl-TBZ and [(3)H]-DTBZ binding. Compound 5 exhibited a better affinity for the vesicular monoamine transporter (K(i)=8.68+/-1.26 nM and 7.01+/-0.07 nM, respectively), which may be a good lead compound for further structural modification to develop useful probes for VMAT2.
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, Beijing, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Jingying
authors.initials: J
authors.lastname: Liu
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
mesh_terms: D000818:Animals; D007457:Iodine Radioisotopes / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D014316:Tritium / Q000737:chemistry; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D050493:Vesicular Monoamine Transport Proteins; D014316:Tritium; C032811:dihydrotetrabenazine; D013747:Tetrabenazine