Plasma drug and homovanillic acid levels in psychotic patients receiving neuroleptics.

Plasma neuroleptic and homovanillic acid (HVA) levels are reported for a group of psychotic subjects exhibiting clinical improvement in response to neuroleptic medication. Clinically effective plasma neuroleptic levels, measured by a radioreceptor assay and expressed as either nanomolar concentration of parent drug or as haloperidol equivalents, were different for the seven neuroleptics tested. Plasma HVA, measured by high-pressure liquid chromatography with electrochemical detection (LCEC), increased in response to initiation of neuroleptic treatment and decreased when neuroleptic medication was withdrawn. No correlations were found between plasma neuroleptic level and HVA level or between HVA level and clinical response. Mean therapeutic plasma levels of neuroleptics, expressed as nanomolar concentration of parent drug, correlated with the potencies of the same drug in displacing 3H-dopamine from D-1 and D-2 receptors in rat striatal membranes. This represents the first report that clinically measured plasma concentrations are high enough to displace dopamine from its specific receptors in the CNS.