- 作者: Hugo F Miranda, Viviana Noriega, Pilar Zanetta, Juan Carlos Prieto, Juan Carlos Prieto-Rayo, Nicolas Aranda, Fernando Sierralta
- 作者服務機構: Pharmacology Program, ICBM, Faculty of Medicine, Universidad de Chile, Independencia , Santiago, Chile
- 中文摘要: --
- 英文摘要:
Background:
Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine,and tramadol was evaluated.
Results:
The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and entanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with
partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes.
Conclusion:
These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity. - 中文關鍵字: --
- 英文關鍵字: Interaction opioid-opioid, Acetic acid writhing test, Hot plate assay, Isobolographic analysis,Synergism