Relationship between analgesia and respiratory depression for mu opioid receptor agonists in mice

Abstract

The relationship between analgesic activity, measured as the hot plate reaction time, and respiratory depression, measured as ventilatory frequency, was investigated in mice for a variety of mu opioid receptor agonists with differing selectivities for mu receptors compared with delta receptors. There was a weak correlation between analgesia and respiratory depression for opioids with the greatest selectivity for mu opioid receptors compared with delta receptors, such as alfentanil. The strength of the correlation increased for opioids which had greater delta receptor activity, such as morphine and fentanyl. Etorphine, which has almost equal affinity for mu, delta and, incidentally, kappa receptors, showed a strong correlation between analgesia and respiratory depression. We conclude that the predictability of the degree of respiratory depression produced by a given analgesic dose of an opioid appears to decrease with its selectivity for mu opioid receptors, at least in the mouse.