Typical antipsychotics exhibit inverse agonist activity at rat dopamine D1-like receptors expressed in Sf9 cells

Eur J Pharmacol. 2001 May 25;420(2-3):73-82. doi: 10.1016/s0014-2999(01)00982-7.

Abstract

The baculovirus system has been used to express the rat dopamine D1 receptors in Spodoptera frugiperda (Sf9) cells. A panel of typical antipsychotics including, alpha-flupenthixol, fluphenazine and thioridizine were found to inhibit dopamine-dependent stimulation of adenylyl cyclase. However, these compounds were also found to inhibit adenylyl cyclase activity in the absence of agonist in Sf9 cells expressing dopamine D1-like receptors. Therefore, these nonselective dopamine receptor compounds displayed negative intrinsic or inverse agonist activity. None of the compounds tested were neutral antagonists.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / drug effects
  • Adenylyl Cyclases / metabolism
  • Animals
  • Antipsychotic Agents / pharmacology*
  • Baculoviridae / genetics
  • Binding, Competitive
  • Cell Line
  • Dopamine / pharmacology
  • Dopamine Agonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression
  • Genetic Vectors / genetics
  • Ligands
  • Radioligand Assay
  • Rats
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / physiology*
  • Receptors, Dopamine D5
  • Spodoptera

Substances

  • Antipsychotic Agents
  • Dopamine Agonists
  • Drd5 protein, rat
  • Ligands
  • Receptors, Dopamine D1
  • Receptors, Dopamine D5
  • Adenylyl Cyclases
  • Dopamine