ALPHA(2)-ADRENOCEPTORS VS IMIDAZOLINE RECEPTORS - IMPLICATIONS FOR ALPHA(2)-MEDIATED ANALGESIA AND OTHER NON-CARDIOVASCULAR THERAPEUTIC USES

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 never therapeutic agents. The present review focuses on alpha(2)-adrenoceptor subtype/imidazoline diversity as a target for analgesic (and other CNS) drug discovery.