Interactions between the lipophilic opioid sufentanil and clonidine in rats after spinal application.
BACKGROUND
Alpha2-adrenoceptor agonists, such as clonidine, can potentiate the analgesic properties of spinal opioids. In order to further extend this observation to highly lipophilic and potent spinally acting opioids, we tested the interactions between clonidine and sufentanil after both epidural and intrathecal administration in rats.


METHODS
The rats were equipped with spinal catheters. Antinociceptive testing 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) sufentanil, 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 addition of clonidine results in activity; 3) In a particular dose-range of sufentanil, there is a direct relationship between the doses of sufentanil 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 contribution of clonidine is minimal at high, intrinsic active doses of sufentanil.
Meert
T F
TF
Janssen Research Foundation, Department of Neuropsychopharmacology, Beerse, Belgium.
De Kock
M
M
D015360:Analgesia, Epidural; D000818:Animals; D001767:Blinking / Q000187:drug effects; D002408:Catheters, Indwelling; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D004357:Drug Synergism; D007278:Injections, Spinal; D009129:Muscle Tonus / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012026:Reflex, Stretch / Q000187:drug effects; D017409:Sufentanil / Q000008:administration & dosage / Q000494:pharmacology*
D004338:Drug Combinations; D017409:Sufentanil; D003000:Clonidine