ABSTRACT
INTRODUCTION a2 Agonists are widely known for their use in the management of hypertensive disorders. These agents have also been found useful in anesthetic and pain management applications. Three a2 agonists are clinically available in the United States: clonidine, tizanidine, and dexmedetomidine. These are imidazolines with varying affinities for a2 receptors, dexmedetomidine being much more selective in binding the a2 receptor as compared with clonidine. These agents act via binding to G protein-linked receptors of three types: a2A, a2B, and a2C. These receptors have been found in both presynaptic and postsynaptic locations, and are distributed centrally and peripherally. Presynaptic activation of a2 receptors may inhibit release of pronociceptive substances such as substance P and calcitonin generelated peptide from afferent nerves. Many of the clinical analgesic effects of a2 agonists are mediated by activation of receptors in the dorsal horn of the spinal cord resulting in decreased transmission of nerve impulses via wide dynamic range neurons. Activation of receptors in supraspinal sites may also result in analgesia via activation of descending inhibitory pathways.
