Differential effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on various 5-HT receptor binding sites in the rat brain

Neuropharmacology. 1994 Mar-Apr;33(3-4):423-31. doi: 10.1016/0028-3908(94)90072-8.


The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an alkylating agent producing irreversible blockade of various membrane bound receptors in brain, were investigated on four different types of serotonin receptors, 5-HT1A, 5-HT1B, 5-HT2A and 5-HT3, in various brain regions in the rat. In addition, the fate of central benzodiazepine- and "R"-zacopride-specific binding sites was also examined in rats treated with EEDQ. Membrane binding assays and/or quantitative autoradiography with appropriate radioligands indicated that EEDQ inactivated 5-HT1A, 5-HT1B and 5-HT2A sites, but was poorly active on 5-HT3, benzodiazepine and "R" sites. Among the receptors affected by EEDQ, hippocampal 5-HT1A sites were the most sensitive to the alkylating agent (ID50 approximately 1 mg/kg i.p.), followed by the cortical 5-HT2A (ID50 approximately 3 mg/kg i.p.) and the striatal 5-HT1B (ID50 approximately 6 mg/kg i.p.) sites. Pretreatment by selective ligands partially protected hippocampal 5-HT1A sites from irreversible inactivation by EEDQ (10 mg/kg i.p.) with the following order of efficacy: WAY 100635 > spiperone > BMY 7378 > ipsapirone. Similarly, pretreatment by spiperone (5 mg/kg i.p.) also reduced the ability of EEDQ to inactivated cortical 5-HT2A receptors. Analyses of the time-course recovery of respective binding sites after EEDQ administration showed that the turnover rate of 5-HT1A sites did not significantly differ in the dorsal raphe nucleus and in various forebrain areas (hippocampus, septum, cerebral cortex; half-life: approximately 4 days), but was lower than that of cortical 5-HT2A sites (half-life: 2.9 days).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Benzamides / pharmacology
  • Brain Chemistry / drug effects*
  • Bridged Bicyclo Compounds / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Flunitrazepam / pharmacology
  • GTP-Binding Proteins / metabolism
  • In Vitro Techniques
  • Ion Channel Gating / drug effects
  • Ligands
  • Male
  • Membranes / drug effects
  • Membranes / metabolism
  • Nerve Tissue Proteins / metabolism
  • Quinolines / pharmacology*
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects*
  • Serotonin / metabolism
  • Serotonin Antagonists / pharmacology*
  • Stereoisomerism


  • Benzamides
  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Ligands
  • Nerve Tissue Proteins
  • Quinolines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin
  • EEDQ
  • Flunitrazepam
  • zacopride
  • GTP-Binding Proteins