title: In vitro and in vivo binding of (E)- and (Z)-N-(iodoallyl)spiperone to dopamine D2 and serotonin 5-HT2 neuroreceptors.
abstract: Apparent affinities (Ki) of (E)- and (Z)-N-(iodoallyl)spiperone [E)- and (Z)-NIASP) for dopamine D2 and serotonin 5-HT2 receptors were determined in competition binding assays. (Z)-NIASP (Ki 0.35 nM, D2; Ki 1.75 nM, 5-HT2) proved slightly more potent and selective for D2 sites in vitro than (E)-NIASP (Ki 0.72 nM, D2; Ki 1.14 nM, 5-HT2). In vivo, radioiodinated (E)- and (Z)-[125I]-NIASP showed regional distributions in mouse brain which are consonant with prolonged binding to dopamine D2 receptors accompanied by a minor serotonergic component of shorter duration. Stereoselective, dose-dependent blockade of (E)-[125I]-NIASP uptake was found for drugs binding to dopamine D2 sites, while drugs selective for serotonin 5-HT2, alpha 1-adrenergic and dopamine D1 receptors did not inhibit radioligand binding 2 hr postinjection. Specific binding in striatal tissue was essentially irreversible over the time course of the study, and (E)-[125I]-NIASP gave a striatal to cerebellar tissue radioactivity concentration of 16.9 to 1 at 6 hr postinjection. Thus, (E)-[125I]-NIASP binds with high selectivity and specificity to dopamine D2 sites in vivo.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205.
authors.forename: J R
authors.initials: JR
authors.lastname: Lever
authors.forename: U A
authors.initials: UA
authors.lastname: Scheffel
authors.forename: M
authors.initials: M
authors.lastname: Stathis
authors.forename: J L
authors.initials: JL
authors.lastname: Musachio
authors.forename: H N
authors.initials: HN
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D046508:Culture Techniques; D005625:Frontal Lobe / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009830:Olfactory Bulb / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D008024:Ligands; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; C064765:N-(iodoallyl)spiperone; D013134:Spiperone