mu-Opioid receptor activation and noradrenaline transport inhibition by tapentadol in rat single locus coeruleus neurons

作者：Sadeghi Mahsa; Tzschentke Thomas M; Christie MacDonald J^*

来源：British Journal of Pharmacology, 2015, 172(2): 460-468.

DOI：10.1111/bph.12566

• tapentadol
• noradrenalin reuptake inhibitor
• opioid receptor agonist
• locus coeruleus
• GIRK channels
• K(IR)3
• x

Background and PurposeTapentadol is a novel analgesic that combines moderate -opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule. Both mechanisms of action are involved in producing analgesia; however, the potency and efficacy of tapentadol in individual neurons has not been characterized.
Experimental ApproachWhole-cell patch-clamp recordings of G-protein-coupled inwardly rectifying K+ (K(IR)3.x) currents were made from rat locus coeruleus neurons in brain slices to investigate the potency and relative efficacy of tapentadol and compare its intrinsic activity with other clinically used opioids.
Key ResultsTapentadol showed agonist activity at receptors and was approximately six times less potent than morphine with respect to K(IR)3.x current modulation. The intrinsic activity of tapentadol was lower than [Met]enkephalin, morphine and oxycodone, but higher than buprenorphine and pentazocine. Tapentadol inhibited the noradrenaline transporter (NAT) with potency similar to that at receptors. The interaction between these two mechanisms of action was additive in individual LC neurons.
Conclusions and ImplicationsTapentadol displays similar potency for both mu receptor activation and NAT inhibition in functioning neurons. The intrinsic activity of tapentadol at the receptor lies between that of buprenorphine and oxycodone, potentially explaining the favourable profile of side effects, related to receptors.
Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit

• 出版日期2015-1