Acute and chronic effects of neuroleptic drugs on plasma and brain homovanilic acid in the rat

Abstract

In the rat, the acute administration of the neuroleptic drug, haloperidol, produces a parallel increase in brain and plasma concentrations of the dopamine metabolite, homovanillic acid (HVA). The effect of other neuroleptic drugs, which may differ from haloperidol in their central and peripheral actions, on brain and plasma HVA has not been systematically investigated. Therefore, in this report we examine the acute effects of six different neuroleptic drugs, representing most major chemical classes of these drugs, on plasma and brain concentrations of HVA. Metoclopramide, fluphenazine, loxapine, and molindone produce parallel increases in brain and plasma HVA which closely resemble those produced by haloperidol. Compared to these neuroleptics, chlorpromazine produces a much greater increase in plasma HVA but a similar effect on brain HVA. The large chlorpromazine-induced increase in plasma HVA suggests that this drug alters peripheral production or clearance of HVA, perhaps via blockade of peripheral α-receptors. Of the available neuroleptics, sulpiride is one of the most specific and potent at blocking the dopamine vascular receptor. Administration of high doses of sulpiride produces only modest increases in both plasma and brain HVA, suggesting that blockade of peripheral dopamine receptors does not substantially alter peripheral clearance of HVA. After chronic administration of haloperidol for up to 21 days, plasma HVA continued to reflect the brain HVA response to drug administration.