title: In vitro and in vivo evaluation of N-{2-[4-(3-Cyanopyridin-2-yl)piperazin-1-yl]ethyl}-3-[(11) C]methoxybenz-amide, a positron emission tomography (PET) radioligand for dopamine D4 receptors, in rodents.
abstract: The D4 dopamine receptor belongs to the D2 -like family of dopamine receptors, and its exact regional distribution in the central nervous system is still a matter of considerable debate. The availability of a selective radioligand for the D4 receptor with suitable properties for positron emission tomography (PET) would help resolve issues of D4 receptor localization in the brain, and the presumed diurnal change of expressed protein in the eye and pineal gland. We report here on in vitro and in vivo characteristics of the high-affinity D4 receptor-selective ligand N-{2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl}-3-[(11) C]methoxybenzamide ([(11) C]2) in rat. The results provide new insights on the in vitro properties that a brain PET dopamine D4 radioligand should possess in order to have improved in vivo utility in rodents.
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari 'A. Moro', via Orabona, 4, IT-70125 Bari.
authors.forename: Marcello
authors.initials: M
authors.lastname: Leopoldo
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Selivanova
authors.forename: Adrienne
authors.initials: A
authors.lastname: Müller
authors.forename: Enza
authors.initials: E
authors.lastname: Lacivita
authors.forename: John A
authors.initials: JA
authors.lastname: Schetz
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
mesh_terms: D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000378:metabolism / Q000494:pharmacology*; D018938:Caco-2 Cells; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D050638:Receptors, Dopamine D4 / Q000378:metabolism*
chemical_list: D001549:Benzamides; C553262:N-(2-(4-(3-cyanopyridin-2-yl)piperazin-1-yl)ethyl)-3-methoxybenzamide; D010879:Piperazines; D050638:Receptors, Dopamine D4
keywords: Dopamine D4 receptors; G-Protein-coupled receptors (GPCR); Piperazine, 1-aryl-; Positron emission tomography (PET); Rodent