INTERACTIONS BETWEEN THE LIPOPHILIC OPIOID SUFENTANIL AND CLONIDINE IN RATS AFTER SPINAL APPLICATION

Background. Alpha(2)-adrenoceptor agonists, such as clonidine. can pot entiate the analgesic properties of spinal opioids. In order to furthe r extend this observation to highly lipophilic and potent spinally act ing opioids, we tested the interactions between clonidine and sufentan il after both epidural and intrathecal administration in rats. Methods . The rats were equipped with spinal catheters. Antinociceptive testin g was performed with the Tail Withdrawal Reaction test. Dose-response functions of sufentanil, clonidine and combinations of clonidine plus sufentanil were determined. Results. These indicated that 1) sufentani l, but not clonidine alone, results in a dose-related antinociception after both the epidural and the intrathecal route of administration; 2 ) In combination with normally inactive doses of sufentanil, the addit ion of clonidine results in activity; 3) In a particular dose-range of sufentanil, there is a direct relationship between the doses of sufen tanil and clonidine needed to produce antinociception; 4) Even at very high doses of clonidine, a minimal amount of sufentanil is needed to produce antinociception and 5) At the conditions tested here, the cont ribution of clonidine is minimal at high, intrinsic active doses of su fentanil.