Abstract

It is generally accepted that analgesia induced by central analgesics is mediated through the mu-receptor. However, it still remains open to question as to whether or not the mu- and/or the delta-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 delta-receptor is able to attenuate sufentanil-related respiratory depression was tested in the dog. High dose (20 micrograms kg-1) sufentanil-induced respiratory impairment could be reversed by selective NTI-antagonism in a dose-related fashion (40-80-160 micrograms kg-1) increasing PaO2 from 57 to 81 mmHg and lowering PaCO2 from 52.1 to 49.2 mmHg. NTB-antagonism (40-80-160 micrograms kg-1) increased PaO2 from 48.4 to 91.2 mmHg 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 microV in the NTI- and 8.8 microV to 1.3 microV in the NTB-group) which was only partially reversed by NTI (2.6 microV) and NTB (2.3 microV) respectively. The results suggest that delta-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 delta-antagonists may be of clinical interest in reversing the respiratory depressant effect of potent opioids while maintaining analgesia.