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 predict response to neuroleptic treatment in schizophrenic patients. In several clinical studies, HVA levels have been shown to have a positive relationship with symptom severity and to decline over time upon treatment with antipsychotic agents. The magnitude of this decline appears to be related to the degree of symptom reduction in patients so treated. However, administration of dopamine postsynaptic antagonists should be expected to increase synaptic dopamine availability, thereby increasing HVA concentrations, according to traditional models of drug action. While in some studies, this appears to be the case, we saw no evidence 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 peak haloperidol levels. Baseline HVA levels of 51.6 +/- 3.83 pmoles/ml and 56.8 +/- 5.70 pmoles/ml (after 4 mg and 10 mg., respectively) declined to minima of 35.6 +/- 1.67 pmoles/ml and 26.3 +/- 5.34 pmoles/ml respectively, at 3-4 hours after haloperidol administration. A trend was 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. The shape of both curves did not appear to be substantially different than expected on the basis of diurnal variation. These preliminary findings support the concept that dopamine turnover in humans is not increased and may be decreased by short-term administration of conventional neuroleptics.