A simple and sensitive radioreceptor assay for antischizophrenic drugs in blood

THE neuroleptics, comprised primarily of phenothiazines, butyrophenones and thioxanthenes, represent the major drugs used in treating schizophrenic symptoms. For several reasons, routine monitoring of patient blood levels of neuroleptics would be desirable. The dose requirement for therapeutic response varies markedly, related in major part to a wide range in blood levels ^1-4. Because the severe motor side effect of tardive dyskinesia ⁵ may be very long-lasting and is apparently dose related, patients should be maintained on the lowest dose required for therapeutic efficacy ^5,6. While blood levels must exceed a threshold to elicit symptomatic improvement, too high a blood level may reduce the therapeutic response ^7-9. The available assays for plasma neuroleptics, including gas chromatography, fluorimetry, formation of radiolabelled derivatives ^4,10-14 and radioimmunoassay^15,16 have not attained routine clinical use because of technical complexities or restrictions of specificity to single drugs. We describe here an assay for neuroleptics based on competition for dopamine receptor binding which is simple, sensitive, specific and suitable for routine clinical application.