title: Opioid-induced respiratory depression and analgesia may be mediated by different subreceptors.
abstract: 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.
authors.affiliation: Department of Vascular Surgery and Renal Transplantation, Heinrich-Heine University, Düsseldorf, FRG.
authors.forename: E
authors.initials: E
authors.lastname: Freye
authors.forename: M
authors.initials: M
authors.lastname: Schnitzler
authors.forename: G
authors.initials: G
authors.lastname: Schenk
mesh_terms: 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*
chemical_list: 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