Dopamine displaces [3H]domperidone from high-affinity sites of the dopamine D2 receptor, but not [3H]raclopride or [3H]spiperone in isotonic medium: Implications for human positron emission tomography

Synapse. 2003 Sep 15;49(4):209-15. doi: 10.1002/syn.10232.


Because the high-affinity state of the dopamine D2 receptor, D2High, is the functional state of the receptor, has a role in demarcating typical from atypical antipsychotics, and is markedly elevated in amphetamine-sensitized rats, it is important to have a method for the convenient detection of this state by a ligand. The present data show that, in contrast to [(3)H]spiperone or [(3)H]raclopride, [(3)H]domperidone labels D2High sites in the presence of isotonic NaCl in either striatum or cloned D2Long receptors, yielding a dopamine dissociation constant (1.75 nM) in agreement with that found with [(3)H]dopamine. Increased labeling of D2High sites occurred with [(3)H]domperidone after severe disruption of the cells, suggesting that [(3)H]domperidone has better access to the D2 receptor from the cytoplasmic aspect of the cell membrane. The density of the [(3)H]domperidone-labeled D2 receptors was the same as that of the [(3)H]raclopride-labeled D2 receptors, but twice the density of [(3)H]spiperone sites for human cloned D2Long receptors, compatible with the monomer-dimer concept of the D2 receptor. [(3)H]domperidone readily labels the D2High sites in postmortem human brain homogenates. Although [(3)H]spiperone or [(3)H]raclopride can occupy D2High sites, the inability of 1-10 nM dopamine to displace these ligands under isotonic conditions suggests that these ligands may not be suitable for monitoring the physiological high-affinity state of the dopamine D2 receptor by means of [(11)C]methylspiperone or [(11)C]raclopride in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Domperidone / pharmacokinetics
  • Domperidone / pharmacology*
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacokinetics
  • Dopamine Antagonists / pharmacology*
  • Isotonic Solutions
  • Raclopride / pharmacokinetics
  • Raclopride / pharmacology*
  • Rats
  • Receptors, Dopamine D2 / metabolism*
  • Sodium / metabolism
  • Spiperone / pharmacokinetics
  • Spiperone / pharmacology*
  • Tomography, Emission-Computed*
  • Tritium


  • Dopamine Antagonists
  • Isotonic Solutions
  • Receptors, Dopamine D2
  • Tritium
  • Raclopride
  • Spiperone
  • Domperidone
  • Sodium
  • Dopamine