title: Effects of dopaminergic drug treatments on in vivo radioligand binding to brain vesicular monoamine transporters.
abstract: The effects of various dopaminergic drug treatments on the in vivo regional brain distribution of high-affinity radioligands ([11C]dihydrotetrabenazine and [11C]methoxytetrabenazine) for the rat brain vesicular monoamine transporter (VMAT2) were determined. Acute treatments with reserpine (2 mg/kg i.p.), tetrabenazine (10 mg/kg i.v.) or related benzoisoquinolines significantly reduced radiotracer binding in vivo. In contrast, radiotracer distributions remained unchanged after treatments with other dopaminergic drugs, whether given by single injection (haloperidol, 1 mg/kg i.p., pargyline 80 mg/kg), repeatedly (pargyline, 80 mg/kg s.c., 14 days), or by continuous infusion (deprenyl, 10 mg/kg/day, 5 days; L-DOPA methyl ester 100 mg/kg/day, 5 days). Repeated injections of tetrabenazine (5 mg/kg i.p., twice daily, 3 days) did not alter in vivo radioligand binding measured after allowing drug washout from the brain. These studies support the proposal that in vivo PET imaging of VMAT2 radioligands in patients with extrapyramidal movement disorders will not be affected by concurrent use of L-DOPA or deprenyl.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Kilbourn
authors.forename: K A
authors.initials: KA
authors.lastname: Frey
authors.forename: T
authors.initials: T
authors.lastname: Vander Borght
authors.forename: P S
authors.initials: PS
authors.lastname: Sherman
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D019556:COS Cells; D002250:Carbon Radioisotopes; D015259:Dopamine Agents / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D009479:Neuropeptides; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
chemical_list: D002250:Carbon Radioisotopes; D015259:Dopamine Agents; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C493453:Slc18a2 protein, mouse; C493454:Slc18a2 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C084867:5-O-methyldihydrotetrabenazine; C032811:dihydrotetrabenazine; D013747:Tetrabenazine