The delta receptor is involved in sufentanil-induced respiratory depression-opioid subreceptors mediate different effects

It is generally accepted that analgesia induced by central analgesics is mediated through the μ-receptor. However, it still remains open to question as to whether or not the μ- and/or the δ-receptor site is mainly involved in the mediation of opioid-related respiratory impairment. Using a highly selective antagonist, naltrindole (NTI), or its benzofuran analogue naltriben (NTB), the hypothesis that competitive antagonism at the δ-receptor is able to attenuate sufentanil-related respiratory depression was tested in the dog. High dose (20 μg kg^-1) sufentanil-induced respiratory impairment could be reversed by selective NTI-antagonism in a dose-related fashion (40-80-160 μg kg^-1) increasing Pao₂ from 57 to 81 mmHg and lowering Paco₂ from 52.1 to 49.2mmHg. NTB-antagonism (40-80-160 μg kg^-1) increased Pao₂ from 48.4 to 91.2mmHg and reduced Paco₂ from 46.9 to 37.6 mmHg. Simultaneously, somatosensory-evoked potentials (SEP) were used to quantify the opioid-induced attenuation and the reversal of afferent sensory input to pain modulating centres in the CNS. Sufentanil induced a significant depression (P<0.01) of amplitude height of the SEP (13.9 to 0.9 μV in the NTI- and 8.8μV to 1.3μV in the NTB-group) which was only partially reversed by NTI (2.6μV) and NTB (2.3 μV) respectively. The results suggest that δ-receptors are involved in sufentanil-related respiratory impairment. These receptors play a minor role in opioid-induced attenuation of sensory input to the brain. Highly selective δ-antagonists may be of clinical interest in reversing the respiratory depressant effect of potent opioids while maintaining analgesia.