Potentiation of the analgesic properties of XXXX -like opioids with alpha 2-adrenoceptor agonists in @entity35 .

@entity1338 @entity681 @entity1337 @entity4931 @entity1510 @entity9006 @entity4763 @entity35 @entity6948 @entity8998 @entity3575
BACKGROUND: Data on the analgesic properties of alpha 2 agonists and their interactions with opioids are conflicting. Experiments were conducted in @entity35 to evaluate whether various available alpha 2 agonists can potentiate the analgesic properties of opioids and to determine the route of administration needed for optimal interaction. METHODS: The tail-withdrawal reaction test was used as an @entity1337 assay. In separate experiments, the interactions between systemic (subcutaneous, intravenous, and intraperitoneal) and spinally (epidural and intrathecal) administered alpha 2 agonists and opioids were evaluated. The antagonism of @entity8998 plus @entity3575 with @entity1510 and/or @entity9006 also was studied. RESULTS: All alpha 2 agonists tested, when injected subcutaneously with @entity3575 , potentiated the opioid-induced @entity1337 . In terms of a reduction of the amount of @entity3575 needed to produce a deep surgical @entity1337 (tail-withdrawal reaction latency > or = 10 s) over more than 2 h, the relative order of potency of the alpha 2 agonists tested was: @entity8998 > @entity6948 > @entity4763 > @entity1338 > @entity4931 . For some of these alpha 2 agonists there was a biphasic effect: at the larger doses tested, a reduction in the @entity3575 potentiation was present. The potentiation of the opioid activity with alpha 2 agonists was also demonstrated in terms of a longer duration of @entity1337 after combined treatment with fixed doses of opioids. The interaction between the alpha 2 agonists and the opioids remained present when a more profound criterion of @entity1337 (tail-withdrawal reaction latency > or = 30 s) was used. Furthermore, the interactions between the alpha 2 agonists tested and @entity3575 or @entity681 appeared to be independent of the route of administration. Potentiations were observed after simultaneous subcutaneous injections of both groups of compounds, after the combination of intraperitoneal (alpha 2 agonist) plus subcutaneous (opioid), intravenous (alpha 2 agonist) plus epidural (opioid) and simultaneous epidural or intrathecal administrations. With regard to antagonism of the analgesic activity of combined treatment with alpha 2 agonists plus opioids, @entity1510 provided total antagonism, whereas the alpha 2 antagonist @entity9006 overcame only the alpha 2 agonist-induced potentiation of @entity3575 . CONCLUSIONS: The tested alpha 2 agonists can potentiate the analgesic properties of opioids, but they have no intrinsic antinociceptive effects on spinal reflexes on their own. The potentiating activities of the alpha 2 agonists could be measured both in terms of a reduction of the amount of opioid needed to reach a particular level of @entity1337 and in terms of a longer duration of @entity1337 with a fixed dose of the opioid. The potentiations were observed with various alpha 2 agonists and opioids and appeared independent of the routes of administration.
