title: Alpha 2-adrenoceptors vs. imidazoline receptors: implications for alpha 2-mediated analgesia and other non-cardiovascular therapeutic uses.
abstract: 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.
authors: R.W. Johnson Pharmaceutical Research Institute, PA 19477-0776.
authors: E E
authors: EE
authors: Codd
authors: J B
authors: JB
authors: Press
authors: R B
authors: RB
authors: Raffa
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology; D011955:Receptors, Drug / Q000819:agonists / Q000187:drug effects* / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000700:Analgesics; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug