Table 3.
Article Highlights
| Article highlights |
|---|
| In terms of analgesic response, the main relevant receptor for most commonly-used opioids is MOR (μ-opioid receptor). Thus, when considering the balance between analgesia and opioid-typical adverse effects, the opioids are rather mono-mechanistic |
| In contrast, tapentadol’s analgesic effect results from the combined contributions of an opioid and a non-opioid mechanism of action |
| Tapentadol’s dual opioid (MOR) and non-opioid (norepinephrine reuptake inhibition; NRI) mechanisms of action combine in a complementary and synergistic manner to produce an antinociceptive effect (analgesia) in animal models, but in less than a synergistic manner to produce the adverse effect of constipation. The question is: to what extent does the opioid component contribute to analgesia on the one hand, and to adverse effects on the other hand? |
| We here estimate, using drug–receptor theory and several different approaches, the μ-load of tapentadol for two classic opioid adverse effects (constipation and respiratory depression) |
| The calculations confirm that both components of tapentadol’s mechanism of analgesic action contribute to its therapeutic effect |
| However, unlike mono-mechanistic opioids, the μ-load (the MOR-related effect in comparison to the effect of a pure/classical opioid at equianalgesia) of tapentadol is substantially less than 100% (calculated estimates yield values of ≤ 40%) |
| The μ-load varies somewhat by type of pain (neuropathic and nociceptive) and by type of adverse effect (constipation and respiratory depression) that is considered for the estimation |
| Estimates using clinical trial data yield results similar to the estimates using in vitro and in vivo animal data |
| The results of this analysis are consistent with, and help explain, the favorable clinical characteristics of tapentadol with regards to opioid-induced side effects. Because of the synergistic mechanism of action, tapentadol provides 100% of the analgesic efficacy of a pure strong opioid, but at < 40% of the µ-load |
| The results of our analysis also suggest that for a drug to be a strong analgesic, it does not have to be a strong opioid, and that this distinction is particularly important when considering the side effects of strong analgesics |