Epinephrine increases spinal cord concentrations of [3H]-clonidine hydrochloride in rabbits after epidural infusion

Epinephrine is often given with epidurally administered drugs to prolong and enhance analgesia, which is partly attributed to alpha-adrenergic processes. This investigation evaluates the effect of epinephrine on the distribution of epidurally administered [3H]-clonidine hydrochloride (clonidine HCl) in serum and in the central nervous system. After placing a lumbar epidural catheter via a laminectomy, rabbits were randomly assigned to receive 20 microCi of clonidine HCl with epinephrine (1:200,000) (n = 5) or without (control; n = 5) for 90 min. During the administration, which included bolus and slow infusion, blood samples were collected at 15-min intervals. At the end of the administration, rabbits were perfused with normal saline, leading to exsanguination. Brain and spinal cord tissues were excised for radiometric analysis. In both groups, the concentration of clonidine HCl was greatest in the lumbar cord. Epinephrine further enhanced accumulation of clonidine HCl into the lumbar cord but did not alter the concentration of clonidine HCl in serum, brain, cervical cord, and thoracic cord. We conclude that lumbar administration of epidural clonidine HCl leads to increased concentrations in the lumbar cord, which is further enhanced by epinephrine. The increased spinal cord accumulation of clonidine may be another mechanism by which epinephrine improves epidural analgesia.