title: Antipsychotic radioreceptor assay: a modification identifying selective receptor effects.
abstract: Radioreceptor assays offer the advantage of a single assay that can assess uniform exposure to multiple chemical compounds. The advent of atypical antipsychotic agents has led to new awareness of the multiple receptor subtypes through which antipsychotic agents may exert their effects, and a renewed interest in comparative drug trials of antipsychotics. The objective of this study was to show the development and validation of antipsychotic radioreceptor assays using clonal cell lines stably expressing isolated human receptors. Model assays were developed using the dopamine(2) (D(2)) and D(4) receptors. D(2) and D(4) activities measured by radioreceptor assay in plasma of antipsychotic-treated subjects were highly correlated with high-performance liquid chromatography determinations of antipsychotic concentrations. Similarly, for a variety of typical and atypical antipsychotic agents, the quotients of D(4)/D(2) activity in plasma of antipsychotic-treated subjects were highly correlated with the quotients of D(4)/D(2) affinities of these agents. Valid receptor-selective antipsychotic assays can be established and may have utility for dissecting the in vivo activity of atypical antipsychotics in relation to specific outcomes in clinical trials.
authors.affiliation: Geriatric Psychopharmacology Program, Division of Geriatrics and Neuropsychiatry, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. sweetra@msx.upmc.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Sweet
authors.forename: R A
authors.initials: RA
authors.lastname: Henteleff
authors.forename: K A
authors.initials: KA
authors.lastname: Meinert
authors.forename: M A
authors.initials: MA
authors.lastname: DeMichele
authors.forename: M A
authors.initials: MA
authors.lastname: Kirshner
authors.forename: D A
authors.initials: DA
authors.lastname: Sorisio
authors.forename: B G
authors.initials: BG
authors.lastname: Pollock
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005347:Fibroblasts; D006801:Humans; D010546:Perphenazine / Q000097:blood; D011869:Radioligand Assay / Q000379:methods*; D017448:Receptors, Dopamine D2 / Q000097:blood*; D050638:Receptors, Dopamine D4; D018967:Risperidone / Q000097:blood
chemical_list: D014150:Antipsychotic Agents; C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D010546:Perphenazine; D018967:Risperidone