An endogenous substance with clonidine-like properties: selective binding to imidazole sites in the ventrolateral medulla

Brain Res. 1988 Feb 16;441(1-2):309-18. doi: 10.1016/0006-8993(88)91409-6.


We sought to characterize the interactions of an endogenous clonidine-displacing substance (CDS) with the specific receptor sites to which clonidine and its analogs bind: (a) the non-adrenergic imidazole binding site, which is present in the ventrolateral medulla (VLM) but not the frontal cortex, (b) high-affinity and (c) low-affinity states of the alpha 2-adrenergic receptor, and (d) the alpha 1-adrenergic receptor. CDS, like clonidine, potently and completely inhibited specific p-[3H]aminoclonidine binding to membranes from the VLM or from the frontal cortex. Both CDS and clonidine bound with highest affinity to imidazole binding sites in the VLM, both were 3-fold selective for high-affinity over low-affinity alpha 2-adrenergic receptors, and both exhibited lowest affinity for alpha 1-adrenergic receptors. Unlike clonidine, CDS exhibited 30-fold selectivity for imidazole over alpha 2-adrenergic receptors but showed only a weak preference for alpha 2- over alpha 1-adrenergic receptors, indicating that CDS and clonidine are not identical. We conclude that CDS is an endogenous clonidine-like substance which may be the natural ligand for imidazole binding sites in the VLM. The receptor-binding properties of CDS are consistent with the view that it is a unique and as yet unrecognized compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Cattle
  • Cell Membrane / metabolism
  • Clonidine / metabolism*
  • Imidazoles / isolation & purification
  • Imidazoles / metabolism*
  • Imidazoline Receptors
  • Kinetics
  • Medulla Oblongata / metabolism*
  • Receptors, Adrenergic, alpha / metabolism*
  • Receptors, Adrenergic, alpha-2*


  • Imidazoles
  • Imidazoline Receptors
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, alpha-2
  • Clonidine