The naphtosultam derivative RP 62203 (fananserin) has high affinity for the dopamine D4 receptor

Eur J Pharmacol. 1996 Oct 24;314(1-2):229-33. doi: 10.1016/s0014-2999(96)00554-7.

Abstract

The dopamine D4 receptor is a potential target for novel antipsychotic drugs. Most available compounds with affinity for the dopamine D4 receptor also bind to dopamine D2 receptors. This report describe the affinity of the 5-HT2A receptor antagonist RP 62203 (fananserin) for the human dopamine D4 receptor. Fananserin displaces [3H]spiperone binding to recombinant human dopamine D4 receptors with a Ki of 2.93 nM. This compares with an affinity (Ki) of 0.37 nM for the rat 5-HT2A receptor and of 726 mM for the rat dopamine D2 receptor. [3H]Fananserin can be used to label the recombinant dopamine D4 receptor expressed in Chinese hamster ovary cells with a KD of 0.725 nM. Fananserin is, thus, the first compound to be reported that distinguishes between dopamine D4 and D2 receptors.

MeSH terms

  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cricetinae
  • Cyclic S-Oxides / metabolism*
  • Humans
  • Male
  • Naphthalenes / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D4
  • Receptors, Serotonin / metabolism
  • Serotonin Antagonists / metabolism*

Substances

  • Cyclic S-Oxides
  • DRD4 protein, human
  • Drd4 protein, rat
  • Naphthalenes
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Receptors, Dopamine D4
  • fananserin