Opioid-induced respiratory depression and analgesia may be mediated by different subreceptors.
Use of selective delta opioid antagonists provide evidence that the delta receptor within the brain seems an integrated part in the mediation of respiratory depression induced by a potent analgesic like fentanyl. Low doses of the delta antagonists RX-8008M (3-6 micrograms/kg) as well as ICI 174,864 (3-6 micrograms/kg) reversed fentanyl-related respiratory depression (arterial blood gases) in the unanesthetized canine. Opioid-induced blockade of afferent sensory nerve volleys (amplitude height of the somatosensory-evoked potential) could be reversed only by a high dose (9 micrograms/kg) of RX-8008M. Depression of amplitude height of the SEP could not be reversed by ICI 174,864 over the whole dose range (3-6-9 micrograms/kg). In comparison, naloxone (1-5-10 micrograms/kg) not only reversed depression of PaO2, it also reversed the blockade of afferent sensory nerve impulses in the low (5-micrograms/kg)-dose range. A highly selective delta antagonist may have a therapeutic value in reversing opioid-related respiratory depression, resulting in little or no attenuation of analgesia.
Freye
E
E
Department of Vascular Surgery and Renal Transplantation, Heinrich-Heine University, Düsseldorf, FRG.
Schnitzler
M
M
Schenk
G
G
D000698:Analgesia; D000818:Animals; D004285:Dogs; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005283:Fentanyl / Q000494:pharmacology; D009019:Morphinans / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects*
D009019:Morphinans; D009294:Narcotics; D011957:Receptors, Opioid; C051207:16-methylcyprenorphine; D004743:Enkephalin, Leucine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D005283:Fentanyl