The binding of SCH 39166 and SCH 23390 to 5-HT1C receptors in porcine choroid plexus

Life Sci. 1991;49(20):1505-11. doi: 10.1016/0024-3205(91)90051-c.

Abstract

SCH 39166 is a novel benzonaphthazepine, which has been characterized as a potent and selective D1 antagonist. Recently, its D1 selective benzazepine predecessor, SCH 23390, has been shown to bind to 5-HT1C binding sites in the choroid plexus. Therefore, the present studies were undertaken to determine if SCH 39166 has any measurable affinity for 5-HT1C binding sites. Our results indicate that SCH 39166 exhibited poor affinity for the 5-HT1C receptor, with a Ki of 1327 nM. In contrast, SCH 23390 inhibited [3H]-mesulergine binding to 5-HT1C receptors with a Ki of 30 nM. The non-selective 5-HT antagonist, methysergide, inhibited binding with a Ki of 2.4 nM. Finally, studies with the stereoisomers of SCH 39166 and SCH 23390 demonstrated that stereoselectivity at the 5-HT1C site is significantly less than for the D1 site.

MeSH terms

  • Animals
  • Antiparkinson Agents / metabolism
  • Benzazepines / metabolism*
  • Binding, Competitive
  • Choroid Plexus / metabolism*
  • Dopamine / metabolism
  • Dopamine Antagonists*
  • Ergolines / metabolism
  • Receptors, Serotonin / metabolism*
  • Serotonin Antagonists / metabolism
  • Swine

Substances

  • Antiparkinson Agents
  • Benzazepines
  • Dopamine Antagonists
  • Ergolines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • ecopipam
  • mesulergine
  • Dopamine