title: In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist (11)C-(R,S)-5-hydroxy-2-(di-n-propylamino)tetralin in rodents and nonhuman primate.
abstract: The in vitro autoradiographic binding characteristics as well as in vivo imaging characteristics of a dopamine D2 receptor agonist, (R, S)-2-(N-propyl-N-1'-(11)C-propyl)amino-5-hydroxytetralin ((11)C-5-OH-DPAT), were studied. In (3)H-spiperone assays using rat striata, 5-OH-DPAT exhibited an affinity of IC(50) = 2.5 nM. In vitro autoradiographs in rat brain slices with (11)C-5-OH-DPAT revealed selective binding to the dopaminergic regions in the striata which was displaceable by sulpiride. Varying concentrations of dopamine displaced this selective binding of (11)C-5-OH-DPAT to the striata in rat brain slices. This selective binding to the striata was also removed in the presence of the GTP analog, 5'-guanylylimidodiphosphate, indicative of the binding of (11)C-5-OH-DPAT to the high-affinity state of the D2 receptor. Ex vivo autoradiographic study in rats exhibited selective binding of (11)C-5-OH-DPAT to the striata. A PET study in a rhesus monkey showed selective localization of (11)C-5-OH-DPAT in the striata and the ratio between striata and cerebellum approached approximately 2 at 40 min postinjection.
authors.affiliation: Department of Internal Medicine/Nuclear Medicine, Kettering Medical Center, Wright State University, Dayton, OH 45429, USA. jogeshwar.mukherjee@kmcnetwork.org
authors.forename: J
authors.initials: J
authors.lastname: Mukherjee
authors.forename: T K
authors.initials: TK
authors.lastname: Narayanan
authors.forename: B T
authors.initials: BT
authors.lastname: Christian
authors.forename: B
authors.initials: B
authors.lastname: Shi
authors.forename: K A
authors.initials: KA
authors.lastname: Dunigan
authors.forename: J
authors.initials: J
authors.lastname: Mantil
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D018491:Dopamine Agonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; C011799:5-hydroxy-2-N,N-dipropylaminotetralin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin