The effects of antipsychotics with 5-HT(2C) receptor affinity in behavioral assays selective for 5-HT(2C) receptor antagonist properties of compounds

Eric P.M. Prinssen, Wouter Koek, Mark S. Kleven

Research output: Contribution to journalArticle

24 Scopus citations


Many antipsychotics have marked antagonist effects at 5-hydroxytryptamine (5-HT(2C)) receptors in vitro, which, however, have been difficult to show in behavioral assays. Here, we used two assays - hypolocomotion and hypophagia induced by the 5-HT(2C) receptor agonist 1-(3-chlorophenyl)piperazine (mCPP) - to try to characterize the 5-HT(2C) receptor antagonist properties of antipsychotics in vivo. Clozapine, olanzapine, pipamperone, and trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz-[2,3:6,7]oxepino[4,5-C] pyrrolidino maleate (ORG 5222), modestly, but significantly, attenuated mCPP (10 mg/kg)-induced hypolocomotion. In contrast, risperidone and loxapine were inactive. The putative antipsychotic ORG 5222 significantly attenuated mCPP (5 mg/kg)-induced hypophagia, whereas the other antipsychotics were inactive. Selective antagonists at dopamine D2-like receptors, α1-adrenoceptors, α2-adrenoceptors, or muscarinic receptors were not able to antagonize the effects of mCPP in either assay. The results suggest that mCPP-induced hypolocomotion can be used to characterize the 5-HT(2C) receptor antagonist properties of antipsychotics, whereas mCPP-induced hypophagia appeared to be sensitive only to compounds highly selective for 5-HT(2C) receptors. Together, these assays may help to characterize functional, in vivo, 5-HT(2C) receptor antagonist properties of antipsychotics. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)57-67
Number of pages11
JournalEuropean Journal of Pharmacology
Issue number1
StatePublished - Jan 24 2000
Externally publishedYes



  • 5-HT (5-hydroxytryptamine)
  • 5-HT(2C) receptor
  • Antipsychotic
  • Behavior
  • Food intake
  • Hypolocomotion
  • Hypophagia
  • Locomotor activity
  • Neuroleptic
  • mCPP-(3-chlorophenyl)piperazine
  • serotonin

ASJC Scopus subject areas

  • Pharmacology

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