Differential in vivo inhibition of [3H]nemonapride binding by atypical antipsychotics in rat striatum, olfactory lobes, and frontal cortex

M. B. Assié, N. Consul-Denjean, W. Koek, A. Newman-Tancredi

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Dopamine D2 receptor blockade is thought to be mandatory for antipsychotic action because most of the currently used antipsychotics have high affinity at these receptors. Here, we examined the in vivo binding characteristics of the D2-like receptor antagonist [ 3H]nemonapride in rat brain areas including the striatum, olfactory lobes and frontal cortex and its inhibition by a series of D2 antagonist antipsychotics. In vivo affinity of [3H]nemonapride was similar (apparent Kd value: 0.05 μmol/kg) in all brain regions examined. The estimated number of binding sites was higher in the striatum (66 fmol/mg wet weight) than in the olfactory lobes (28 fmol/mg wet weight) and the frontal cortex (21 fmol/mg wet weight). In the striatum, [3H] nemonapride binding was inhibited in a dose-dependent manner with the following order of potency (ED50, mg/kg): nemonapride (0.04), raclopride (0.13), spiperone and risperidone (0.14), haloperidol (0.21), clozapine (7.2) and thioridazine (9.4); in the olfactory lobes: nemonapride (0.03), raclopride and spiperone (0.09), haloperidol (0.10), risperidone (0.15), thioridazine and clozapine (11); in the frontal cortex, only the high affinity dopamine D 2 antagonist compounds nemonapride (0.05), haloperidol (0.09), and raclopride (0.12) significantly decreased the binding of [3H] nemonapride. The present data suggest that conventional and atypical antipsychotics may be distinguished by their differential occupancy of striatal versus fronto-cortical D2-like receptors in vivo.

Original languageEnglish (US)
Pages (from-to)63-68
Number of pages6
JournalPharmacology
Volume75
Issue number2
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

Keywords

  • D-like receptors
  • Frontal cortex
  • In vivo binding
  • Olfactory lobes
  • [H]nemonapride

ASJC Scopus subject areas

  • Pharmacology

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