Interaction of the D1 receptor antagonist SCH 23390 with the central 5-HT system: radioligand binding studies, measurements of biochemical parameters and effects on L-5-HTP syndrome

J Recept Res. 1988;8(1-4):107-20. doi: 10.3109/10799898809048981.

Abstract

The interaction of SCH 23390 with dopamine (DA) and serotonin (5-HT) systems has been examined in vivo and in vitro. Like selective 5-HT2 blockers, SCH 23390 inhibited in vivo [3H]spiperone binding in the rat frontal cortex (ID50: 1.5 mg/kg) without interacting at D2 sites. SCH 23390 was equipotent to cinanserin and methysergide. In vitro, SCH 23390 inhibited [3H]ketanserin binding to 5-HT2 sites (IC50 = 30 nM). Biochemical parameters linked to DA and 5-HT were not changed excepted in striatum where SCH 23390 increased HVA and DOPAC. In the L-5-HTP syndrome model, SCH 23390 clearly showed antagonism of 5-HT2 receptors. SCH 23390 had weak affinity for 5-HT1B (IC50 = 0.5 microM), 5-HT1A (IC50 = 2.6 microM) and alpha 1-adrenergic receptors (IC50 = 4.4 microM).

MeSH terms

  • 5-Hydroxytryptophan / toxicity*
  • Animals
  • Benzazepines / metabolism
  • Benzazepines / pharmacology*
  • Benzazepines / therapeutic use
  • Binding, Competitive
  • Corpus Striatum / metabolism
  • Dopamine / metabolism
  • Frontal Lobe / metabolism
  • Hippocampus / metabolism
  • Male
  • Movement Disorders / chemically induced*
  • Movement Disorders / drug therapy
  • Rats
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / metabolism
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism
  • Serotonin Antagonists / metabolism

Substances

  • Benzazepines
  • Receptors, Dopamine
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin
  • 5-Hydroxytryptophan
  • Dopamine