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 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.
Freye
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Department of Vascular Surgery and Renal Transplantation, Heinrich-Heine-University Clinics of Düsseldorf, Germany.
Latasch
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Portoghese
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D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D009019:Morphinans / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000187:drug effects* / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D017409:Sufentanil / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D007211:Indoles; D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; D002245:Carbon Dioxide; D009271:Naltrexone; D017409:Sufentanil; C055382:naltrindole; D010100:Oxygen