Alpha 2-adrenoceptors vs. imidazoline receptors: implications for alpha 2-mediated analgesia and other non-cardiovascular therapeutic uses

Life Sci. 1995;56(2):63-74. doi: 10.1016/0024-3205(94)00415-o.


The multiple clinical actions of clonidine have historically been linked to the same receptor (alpha 2-adrenoceptor) due to the belief that clonidine was a selective alpha 2-agonist. However, it is now recognized that clonidine binds with a similar affinity to alpha 2-adrenoceptors and to non-adrenergic imidazoline receptors. These two pharmacological targets (and subtypes of each alpha 2 and imidazoline receptors) provide the basis for a possible separation of cardiovascular and other targeted effects, such as analgesia. Consequently, the design of selective alpha 2-adrenoceptor (subtype) agonists as analgesics devoid of the cardiovascular effects associated with clonidine appears to be a rational approach to novel therapeutic agents. The present review focuses on alpha 2-adrenoceptor subtype/imidazoline diversity as a target for analgesic (and other CNS) drug discovery.

Publication types

  • Review

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists
  • Analgesics / metabolism
  • Analgesics / pharmacology*
  • Animals
  • Humans
  • Imidazoline Receptors
  • Receptors, Adrenergic, alpha-2 / drug effects*
  • Receptors, Adrenergic, alpha-2 / physiology
  • Receptors, Drug / agonists
  • Receptors, Drug / drug effects*
  • Receptors, Drug / physiology


  • Adrenergic alpha-2 Receptor Agonists
  • Analgesics
  • Imidazoline Receptors
  • Receptors, Adrenergic, alpha-2
  • Receptors, Drug