Covariation of alpha 2-adrenoceptor density and function following irreversible antagonism with EEDQ

Br J Pharmacol. 1994 Jul;112(3):855-60. doi: 10.1111/j.1476-5381.1994.tb13158.x.


1. Administration of the irreversible antagonist, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, (EEDQ, 2 mg kg-1, i.p.) to mice reduced binding of [3H]-RX 821002 (2-methoxy-idazoxan) to alpha 2-adrenoceptors in whole mouse brain by 75% 24 h later. The receptor binding returned over time only being reduced by 25% by 16 days post administration; the time taken for binding to return to 50% of control levels was estimated to be 5.25 days. 2. EEDQ administration also resulted in the loss of the sedative effect of the alpha 2-adrenoceptor agonist, medetomidine, measured by the holeboard test of directed exploration and locomotor activity. Agonist-induced sedation returned to control values by 8 days post EEDQ administration. 3. EEDQ administration also resulted in the loss of the hypothermic response to medetomidine (0.1 mg kg-1, i.p.). Medetomidine-induced hypothermia returned to control values by 12 days post EEDQ administration. 4. Pretreatment with the selective alpha 2-adrenoceptor antagonist, RX 821002 (0.1-3.0 mg kg-1, i.p.) 45 min before EEDQ prevented the loss of alpha 2-adrenoceptors as well as the blockade of medetomide-induced sedation and hypothermia by EEDQ. 5. The results of these experiments indicate that there is significant receptor reserve for alpha 2-adrenoceptor-mediated behavioural and physiological responses.

MeSH terms

  • Adrenergic alpha-2 Receptor Antagonists*
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Body Temperature / drug effects
  • Dioxanes / pharmacokinetics
  • Drug Interactions
  • Exploratory Behavior / drug effects
  • Hypnotics and Sedatives / pharmacology
  • Idazoxan / analogs & derivatives
  • Imidazoles / pharmacology
  • Male
  • Medetomidine
  • Mice
  • Motor Activity / drug effects
  • Quinolines / pharmacology*
  • Radioligand Assay
  • Receptors, Adrenergic, alpha-2 / metabolism*


  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Dioxanes
  • Hypnotics and Sedatives
  • Imidazoles
  • Quinolines
  • Receptors, Adrenergic, alpha-2
  • EEDQ
  • 2-methoxyidazoxan
  • Medetomidine
  • Idazoxan