Antipsychotic radioreceptor assay: A modification identifying selective receptor effects

Radioreceptor assays offer the advantage of a single assay that can assess uniform exposure to multiple chemical compounds. The advent of atypical ant ipsychotic agents has led to new awareness of the multiple receptor subtype s through which antipsychotic agents may exert their effects, and a renewed interest in comparative drug trials of antipsychotics. The objective of th is study was to show the development and validation of antipsychotic radior eceptor assays using clonal cell lines stably expressing isolated human rec eptors. Model assays were developed using the dopamine(2) (D-2) and D-4 rec eptors. D-2 and D-4 activities measured by radioreceptor assay in plasma of antipsychotic-treated subjects were highly correlated with highperformance liquid chromatography determinations of antipsychotic concentrations. Simi larly, for a variety of typical and atypical antipsychotic agents, the quot ients 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 h ave utility for dissecting the in vivo activity of atypical antipsychotics in relation to specific outcomes in clinical trials.