Characterization of the binding of SCH 39166 to the five cloned dopamine receptor subtypes

Pharmacol Biochem Behav. 1994 Nov;49(3):567-71. doi: 10.1016/0091-3057(94)90070-1.

Abstract

Characterization studies were conducted on the five cloned dopamine receptor subtypes (D1-D5) using the novel D1-selective antagonist, SCH 39166, as well as other related benzazepines and dopaminergic agents. The results demonstrate that SCH 39166 exhibits saturable, high-affinity binding to the D1 and D5 receptors, but binds with low affinity to the D2, D3, and D4 receptors. In contrast, the D2 antagonist haloperidol showed low affinity for the "D1-like" receptors and high affinity for the "D2-like" receptors. A series of agonists was also evaluated and the D5 receptor subtype displayed a two-site fit for the endogenous agonist dopamine, as well as for the agonist apomorphine. Differences in agonist binding among the D1-like receptors reflect the importance of the nonconserved amino acid substitutions.

MeSH terms

  • Benzazepines / metabolism*
  • Binding, Competitive / drug effects
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cloning, Molecular
  • Dopamine Agonists / metabolism
  • Dopamine Antagonists / metabolism*
  • Humans
  • Radioligand Assay
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3
  • Receptors, Dopamine D4
  • Receptors, Dopamine D5
  • Recombinant Proteins / metabolism

Substances

  • Benzazepines
  • DRD3 protein, human
  • DRD4 protein, human
  • DRD5 protein, human
  • Dopamine Agonists
  • Dopamine Antagonists
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Recombinant Proteins
  • ecopipam
  • Receptors, Dopamine D4
  • Receptors, Dopamine D5