title: Positron emission tomographic analysis of central dopamine D1 receptor binding in normal subjects treated with the atypical neuroleptic, SDZ MAR 327.
abstract: SDZ MAR 327 is a new neuroleptic agent with high in vitro affinity for dopamine D1 and D2 receptors. The goal of this study was to determine the effect of time after SDZ MAR 327 administration on central dopamine D1 receptor occupancy in healthy humans. Positron emission tomography (PET) with the dopamine D1 receptor ligand, [11C] SCH 23390, was performed in 6 male volunteers (age 22-34), in both the drug naive state and at 1, 2 and 4 h after a single oral dose of SDZ MAR 327 (9 mg). The pre and post drug treatment [11C] SCH 23390 dynamic data were analyzed using two different methods, each yielding a parameter proportional to the receptor density: i) a simple regional comparison approximating the specifically bound to free fraction, B/F; and ii) a two compartment, two parameter model yielding the apparent distribution volume DV". With both methods, a metabolite corrected arterial input function was used and the vascular fraction of tissue (Vb) was fixed at a previously determined value of 4%. Method I served as a qualitative comparison of the paired studies and demonstrated little difference between the pre and post drug conditions, method II also confirmed that there was no significant change in binding of [11C] SCH 23390 in the striatum. These data indicate that SDZ MAR 327 produces little if any effect on dopamine D1 receptor binding at the dose used.
authors.affiliation: Division of Nuclear Medicine of the Department of Radiology, Massachusetts General Hospital, and the Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: B T
authors.initials: BT
authors.lastname: Christian
authors.forename: J W
authors.initials: JW
authors.lastname: Babich
authors.forename: E
authors.initials: E
authors.lastname: Livni
authors.forename: N M
authors.initials: NM
authors.lastname: Alpert
authors.forename: A A
authors.initials: AA
authors.lastname: Bonab
authors.forename: L
authors.initials: L
authors.lastname: Munconi
authors.forename: R
authors.initials: R
authors.lastname: Polinski
authors.forename: R H
authors.initials: RH
authors.lastname: Rubin
authors.forename: A J
authors.initials: AJ
authors.lastname: Fischman
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001552:Benzazepines / Q000493:pharmacokinetics; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D004873:Ergolines / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008297:Male; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D014150:Antipsychotic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D004873:Ergolines; D017447:Receptors, Dopamine D1; C110445:SDZ MAR 327