EFFECTS OF SINGLE-DOSE HALOPERIDOL ADMINISTRATION ON PLASMA HOMOVANILLIC-ACID LEVELS IN NORMAL SUBJECTS

Homovanillic acid (HVA), an oxidative metabolite of dopamine, has been shown in a number of studies to reflect severity of symptoms and to p redict response to neuroleptic treatment in schizophrenic patients. In several clinical studies, HVA levels have been shown to have a positi ve relationship with symptom severity and to decline over time upon tr eatment with antipsychotic agents. The magnitude of this decline appea rs to be related to the degree of symptom reduction in patients so tre ated. However, administration of dopamine postsynaptic antagonists sho uld be expected to increase synaptic dopamine availability, thereby in creasing HVA concentrations, according to traditional models of drug a ction. While in some studies, this appears to be the case, we saw no e vidence of an early phase of HVA elevation after administration of 4- and 10-milligram doses of haloperidol to human volunteers. Rather, HVA levels declined during the period of absorption and attainment of pea k haloperidol levels. Baseline HVA levels of 51.6 +/- 3.83 pmoles/ml a nd 56.8 +/- 5.70 pmoles/ml (after 4 mg and 10 mg., respectively) decli ned to minima of 35.6 +/- 1.67 pmoles/ml and 26.3 +/- 5.34 pmoles/ml r espectively, at 3-4 hours after haloperidol administration. A trend wa s noted for the 10-mg dose to produce a greater decline than the 4-mg dose, which was most apparent at 4 hours after drug administration. Th e shape of both cur-ves did not appear to be substantially different t han expected on the basis of diurnal variation. These preliminary find ings support the concept that dopamine turnover in humans is not incre ased and may be decreased by short-term administration of conventional neuroleptics.