[Ethyl-3H]RS-79948-197 alpha2-adrenoceptor autoradiography validation in alpha2-adrenoceptor knockout mice

Eur J Pharmacol. 2004 Aug 30;497(3):301-9. doi: 10.1016/j.ejphar.2004.06.065.


[Ethyl-(3)H][8aR,12aS,13aS]-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-methoxy-12-(ethylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridine ([ethyl-(3)H]RS-79948-197) was evaluated for alpha(2)-adrenoceptor autoradiography in brain sections from wild-type mice and alpha(2A)- and alpha(2ABC)-adrenoceptor knockout mice. Receptor numbers were 83% lower in cortex and 28% lower in caudate putamen of alpha(2A)-knockout mice than in wild-type mice. No specific binding was seen in alpha(2ABC)-knockout mice. [Ethyl-(3)H]RS-79948-197 saturation binding parameters were compared to those of [(3)H]2-(2,3-dihydro-2-methoxy-1,4-benzodioxan-2-yl)-4,5-dihydro-1H-imidazoline ([(3)H]RX821002) and [methyl-(3)H]17alpha-hydroxy-20alpha-yohimban-16beta-carboxylic acid methyl ester ([methyl-(3)H]rauwolscine). [Ethyl-(3)H-]RS-79948-197 detected a larger number of both alpha(2A)- and alpha(2B/C)-adrenoceptors than [(3)H]RX821002, while [methyl-(3)H]rauwolscine only underestimated the number of alpha(2A)-adrenoceptors. Oxymetazoline and prazosin competed for [ethyl-(3)H]RS-79948-197 binding with the expected rank order of affinities. Higher than necessary [ethyl-(3)H]RS-79948-197 concentrations resulted in a rapid increase in non-specific binding. Slow dissociation kinetics, high specific radioactivity and high alpha(2)-adrenoceptor affinity (slightly lower for the alpha(2A)-adrenoceptor than for the other subtypes) confer [ethyl-(3)H]RS-79948-197 distinct advantages compared to [(3)H]RX821002 for detection of alpha(2)-adrenoceptor subtypes in a mixed alpha(2)-adrenoceptor population.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Antagonists*
  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Autoradiography
  • Binding Sites
  • Binding, Competitive
  • Cerebral Cortex / metabolism
  • Idazoxan / analogs & derivatives*
  • Idazoxan / pharmacology
  • In Vitro Techniques
  • Isoquinolines / pharmacology*
  • Ligands
  • Mice
  • Mice, Knockout
  • Naphthyridines / pharmacology*
  • Oxymetazoline / pharmacology
  • Phentolamine / pharmacology
  • Prazosin / pharmacology
  • Putamen / metabolism
  • Radioligand Assay
  • Receptors, Adrenergic, alpha-2 / genetics
  • Receptors, Adrenergic, alpha-2 / metabolism*
  • Tritium
  • Yohimbine / pharmacology


  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Agonists
  • Isoquinolines
  • Ligands
  • Naphthyridines
  • RS 79948-197
  • Receptors, Adrenergic, alpha-2
  • Tritium
  • Yohimbine
  • Oxymetazoline
  • 2-methoxyidazoxan
  • Prazosin
  • Idazoxan
  • Phentolamine