Comparative antidopaminergic properties of thioridazine, mesoridazine and sulforidazine on the corpus striatum.

Published

Journal Article

The functional antidopaminergic potencies of the atypical antipsychotic drug thioridazine (THD), as well as its active metabolites mesoridazine (MES) and sulforidazine (SUL), were assessed by testing their blockade of the inhibitory effects of endogenous dopamine (DA) or apomorphine on the electrically evoked release of radiolabeled DA and acetylcholine (ACh) from perfused rabbit striatal slices. These functional comparisons (reflecting presynaptic and postsynaptic DA receptors, respectively) were correlated with potency estimations of these drugs in competing for D2 DA receptors (i.e., [3H]spiperone binding sites) in rabbit striatal homogenates. Similar orders of potency (SUL greater than MES much greater than THD) were found for blockade of pre- and postsynaptic DA receptors modulating DA and ACh release, respectively, as well as in competing for [3H]spiperone binding sites in the striatum. MES, SUL and haloperidol were 2 to 3 times more potent at DA release modulatory receptors than postsynaptic DA receptors. In contrast, THD was 8 times more potent at antagonizing the apomorphine-induced inhibition of DA release than against apomorphine's effect on ACh release. THD was virtually inactive in antagonizing the inhibition of ACh release induced when nomifensine was used to increase endogenous synaptic DA, despite significantly antagonizing these effects on DA release in the same slices. Together, these data indicate that: 1) MES and SUL are responsible for a significant part of the antidopaminergic effects attributed to THD; 2) THD should produce less cholinergic activation than other neuroleptics; and 3) that nonreceptor-mediated effects at high THD concentrations may mask effects due to receptor blockade.

Full Text

Duke Authors

Cited Authors

  • Niedzwiecki, DM; Cubeddu, LX; Mailman, RB

Published Date

  • July 1, 1989

Published In

Volume / Issue

  • 250 / 1

Start / End Page

  • 117 - 125

PubMed ID

  • 2746491

Pubmed Central ID

  • 2746491

International Standard Serial Number (ISSN)

  • 0022-3565

Language

  • eng

Conference Location

  • United States