[3H]Alnespirone: a novel specific radioligand of 5-HT1A receptors in the rat brain

Eur J Pharmacol. 1997 Oct 22;337(2-3):297-308. doi: 10.1016/s0014-2999(97)01288-0.


Determination of the optimal assay conditions for the specific binding of a tritiated derivative of the novel potential anxiolytic drug alnespirone (S-20499, (+)-4-[N-(5-methoxy-chroman-3-yl)-N-propylamino]butyl-8-azaspiro-( 4,5)-decane-7,9-dione) allowed the demonstration that this radioligand bound with a high affinity (Kd = 0.36 nM) to a homogeneous class of sites in rat hippocampal membranes. The pharmacological properties of [3H]alnespirone specific binding sites matched exactly (r = 0.95) those of 5-HT1A receptors identified with [3H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) as radioligand. Furthermore, membrane binding experiments and autoradiographic labeling of tissue sections showed that the regional distribution of [3H]alnespirone specific binding sites in the rat brain and spinal cord superimposed over that of 5-HT1A receptors specifically labeled by [3H]8-OH-DPAT. However, the differential sensitivity of [3H]alnespirone and [3H]8-OH-DPAT specific binding to various physicochemical effectors (temperature, pH, Mn2+, N-ethyl-maleimide) supports the idea that these two agonist radioligands did not recognize 5-HT1A receptors exactly in the same way. These differences probably account for the reported inability of alnespirone, in contrast to 8-OH-DPAT, to induce some 5-HT1A receptor-mediated behavioural effects in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / metabolism
  • Animals
  • Anti-Anxiety Agents / metabolism*
  • Autoradiography
  • Brain / anatomy & histology
  • Brain / metabolism*
  • Chlorides / pharmacology
  • Ethylmaleimide / pharmacology
  • Guanosine Triphosphate / pharmacology
  • Hydrogen-Ion Concentration
  • Ligands
  • Male
  • Manganese Compounds / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists / metabolism*
  • Spiro Compounds / metabolism*
  • Temperature


  • Anti-Anxiety Agents
  • Chlorides
  • Ligands
  • Manganese Compounds
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • Spiro Compounds
  • alnespirone
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Guanosine Triphosphate
  • Ethylmaleimide
  • manganese chloride