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Antipsychotic radioreceptor assay: a modification identifying selective receptor effects
R A Sweet1, R A Henteleff, K A Meinert
1Geriatric Psychopharmacology Program, Division of Geriatrics and Neuropsychiatry, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. sweetra@msx.upmc.edu
Therapeutic Drug Monitoring
|July 31, 2001
Summary
Radioreceptor assays can now measure antipsychotic drug effects on dopamine receptors D(2) and D(4). These validated assays correlate well with drug levels and affinities, aiding clinical trial analysis.
Area of Science:
- Pharmacology
- Neuroscience
- Assay Development
Background:
- Atypical antipsychotics highlight the importance of multiple receptor subtypes in drug action.
- Comparative drug trials for antipsychotics require precise measurement of drug effects.
- Radioreceptor assays offer a method to assess exposure to multiple compounds simultaneously.
Purpose of the Study:
- To develop and validate radioreceptor assays for antipsychotics.
- To utilize clonal cell lines expressing human dopamine receptors D(2) and D(4).
- To assess the utility of these assays in understanding in vivo antipsychotic activity.
Main Methods:
- Development of model radioreceptor assays using dopamine D(2) and D(4) receptors.
- Stable expression of isolated human receptors in clonal cell lines.
- Measurement of receptor activity in plasma from antipsychotic-treated subjects.
Main Results:
- Radioreceptor assay measurements of D(2) and D(4) activity strongly correlated with HPLC-determined antipsychotic concentrations.
- Quotients of D(4)/D(2) activity in plasma correlated with D(4)/D(2) affinities for various antipsychotics.
- Validated receptor-selective antipsychotic assays were established.
Conclusions:
- Established radioreceptor assays are valid and useful for studying antipsychotic drug activity.
- These assays can help dissect the in vivo effects of atypical antipsychotics.
- The assays may aid in analyzing clinical trial outcomes related to specific receptor interactions.