| First Author | Ozdoğan UK | Year | 2006 |
| Journal | Eur J Pharmacol | Volume | 529 |
| Issue | 1-3 | Pages | 105-13 |
| PubMed ID | 16325800 | Mgi Jnum | J:106379 |
| Mgi Id | MGI:3618424 | Doi | 10.1016/j.ejphar.2005.10.029 |
| Citation | Ozdogan UK, et al. (2006) The analgesic efficacy of partial opioid agonists is increased in mice with targeted inactivation of the alpha2A-adrenoceptor gene. Eur J Pharmacol 529(1-3):105-13 |
| abstractText | Alpha(2A)-Adrenoceptors mediate the antinociceptive effects of alpha(2)-adrenoceptor agonists in mice, and analgesic synergism between noradrenergic and opioidergic mechanisms has been reported to be lacking in mice devoid of functional alpha(2A)-adrenoceptors. We investigated whether the antinociceptive actions of opioid agonists with different efficacy would be altered in mice with targeted inactivation of the alpha(2A)-adrenoceptor gene (alpha(2A)-KO mice). The antinociceptive effects of fentanyl, morphine, buprenorphine and tramadol were assessed using conventional tail-flick and hot-plate assays. Antinociceptive responses to fentanyl were unaltered in the alpha(2A)-KO animals. Morphine analgesia was slightly accentuated in the tail-flick test. The naloxone-sensitive antinociceptive responses to both tested weak partial agonists were very markedly accentuated in both tests. For example, after 40 mg/kg tramadol administration, the tramadol-induced prolongation of tail-flick latency was 86+/-6% of the maximal possible effect (MPE) in alpha(2A)-KO and 22+/-2% of MPE in control mice; prolongation of hot-plate latency was 93+/-5% of MPE in alpha(2A)-KO mice and 8+/-2% of MPE in the controls (P<0.001 for both). The effects of alpha(2A)-KO were mimicked by pretreatment of wild-type control mice with the alpha(2)-adrenoceptor antagonists, atipamezole and yohimbine; the apparent efficacy of tramadol and buprenorphine now approached that of morphine and fentanyl. Other behavioural effects of the tested opioid agonists were not similarly influenced by alpha(2A)-KO. Antagonists of alpha(2A)-adrenoceptors may offer a novel mechanism to augment the antinociceptive actions of partial opioid agonists. |
