Agonist, antagonist, and inverse agonist properties of antipsychotics at human recombinant 5-HT1A receptors expressed in HeLa cells

Cristina Cosi, Wouter Koek

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Agonist and antagonist properties of antipsychotics at human (h) recombinant 5-hydroxytryptamine1A (h5-HT1A) receptor have been examined previously in transfected Chinese hamster ovary (CHO) cells using 5′-O-(3-[35S]thio)-triphosphate ([35S] GTPγS) binding. Na+-dependent [35S] GTPγS binding to membranes from human epithelioid carcinoma (HeLa) cells, expressing 500 fmol/mg protein of h5-HT1A receptor (HA7 cells), appears suitable to characterize not only agonist and antagonist properties of 5-HT1A receptor ligands, but also inverse agonist properties. We therefore examined agonist, antagonist, and inverse agonist activity of antipsychotics at h5-HT1A receptor in HA7 cells. Some antipsychotics had agonist activity and stimulated [35S] GTPγS binding with the following order of efficacy: nemonapride>ziprasidone>clozapine>ocaperidone. Tiospirone and trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7,5]-oxepino- [4,5c]pyrrole (ORG 5222), were more potent h5-HT1A receptor antagonists than raclopride, olanzapine, and risperidone. Haloperidol, chlorpromazine, thioridazine, pimozide, and sertindole showed Na+-dependent inverse agonist activity at h5-HT1A receptor that could be antagonized by (s)-N-tert-butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide [(s)-WAY 100135]. These results are further evidence that interactions with h5-HT1A receptors could play a role in the pharmacological profile of certain antipsychotics, and that Na+ affects the ability to detect inverse agonist activity at h5-HT1A receptors, likely by influencing receptor precoupling. Also, the manner in which compounds interact with 5-HT1A receptors appears to be related to their Kb/Ki ratio.

Original languageEnglish (US)
Pages (from-to)55-62
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number1
StatePublished - Dec 14 2001
Externally publishedYes


  • 5-HT receptor
  • Antipsychotic
  • HA7 cell
  • Inverse agonism
  • [S] GTPγS binding

ASJC Scopus subject areas

  • Pharmacology


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