In vitro biochemical evidence that the psychotomimetics phencyclidine, ketamine and dizocilpine (MK-801) are inactive at cloned human and rat dopamine D2 receptors

Eur J Pharmacol. 2006 Jul 1;540(1-3):53-6. doi: 10.1016/j.ejphar.2006.04.026. Epub 2006 May 3.

Abstract

Dopamine potently increased calcium mobilization in Chinese hamster ovary cells expressing human dopamine D2Long receptors (CHO-D2L cells), and increased guanosine-5'-O-(3-[35S]thio)-triphosphate binding to CHO-D2L cell and rat striatal membranes. These effects of dopamine were blocked by the dopamine D2 receptor antagonist (-)raclopride. In contrast to the findings of a recent controversial study, phencyclidine, ketamine and dizocilpine (MK-801) lacked dopamine D2 receptor full agonist, partial agonist and antagonist activity in these assays, suggesting their psychotomimetic effects, and activity in rodent models of schizophrenia, are associated with N-methyl-d-aspartate receptor blockade rather than a direct interaction with dopamine D2 receptors.

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • CHO Cells
  • Calcium / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cricetinae
  • Cricetulus
  • Dizocilpine Maleate / pharmacology*
  • Dopamine / pharmacology
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Gene Expression / genetics
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Humans
  • Ketamine / pharmacology*
  • Phencyclidine / pharmacology*
  • Raclopride / pharmacology
  • Rats
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Sulfur Radioisotopes

Substances

  • Dopamine Agonists
  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • Sulfur Radioisotopes
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Raclopride
  • Ketamine
  • Dizocilpine Maleate
  • Phencyclidine
  • Calcium
  • Dopamine