Novel selective compounds for the investigation of imidazoline receptors

Ann N Y Acad Sci. 1999 Jun 21:881:81-91. doi: 10.1111/j.1749-6632.1999.tb09344.x.


Over several years our group has sought to synthesize and identify selective ligands for imidazoline (I) receptors, in particular the I2 binding site. As a consequence, [3H]2-(2-benzofuranyl)-2-imidazoline (2BFI) has proved extremely useful for binding and autoradiographic studies. More recently we have synthesized a BU series of compounds and examined these for their affinities for both I1 and I2 binding sites. BU224 (2-(4,5-dihydroimidaz-2-yl)-quinoline) shows high affinity for I2 receptors with a Ki of 2.1 nM. BU226 (2-(4,5-dihydroimidaz-2-yl)-isoquinoline) demonstrated slightly higher affinity (Ki 1.4 nM) for I2 receptors, but overall BU224 displayed greater selectivity for I2 over I1 receptors (832-fold) than BU226 (380-fold). Both compounds showed low (microM) affinity for alpha 2-adrenoceptors. Given BU224's ability to cross the blood brain barrier, we predict that its in vivo effects are likely to be mediated via I2 receptors. Brain dialysis revealed BU224 to dose dependently (0-20 mg/kg i.p.) elevate basal noradrenaline in rat frontal cortex and basal dopamine in striatum. In a rat model of opiate withdrawal, behavioral studies showed that BU224 (10 mg/kg, s.c.) was able to reduce acute weight loss and diarrhea, but not the number of wet dog shakes associated with the withdrawal syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Binding Sites
  • Blood-Brain Barrier
  • Brain / metabolism
  • Clonidine / pharmacokinetics
  • Dogs
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacokinetics*
  • Imidazoline Receptors
  • Morphine Dependence / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Drug / chemistry
  • Receptors, Drug / metabolism*
  • Structure-Activity Relationship
  • Substance Withdrawal Syndrome / metabolism
  • Tritium


  • BU 224
  • Imidazoles
  • Imidazoline Receptors
  • Receptors, Drug
  • Tritium
  • Clonidine