Sufentanil-related respiratory depression and antinociception in the dog. Mediation by different receptor types.
The mu-receptor purportedly is considered the site responsible for the mediation of opioid-related respiratory depression. However, there is no equivocal understanding whether the same site is also responsible for antinociception. For blockade of effects, the selective mu-antagonist beta-funaltrexamine (CAS 72782-05-9, beta-FNA) was given intracerebroventricularly (i.c.v.) prior to increasing doses of sufentanil (CAS 60561-17-3) (3, 6 and 12 micrograms/kg) in the conscious dog. This was followed by the selective delta-antagonist naltrindole (CAS 111555-53-4) (160 micrograms/kg). After one week, using the same dosages and the same animals, saline instead of beta-FNA was given i.c.v., again followed by sufentanil and naltrindole. Arterial blood gases (paO2, paCO2) were used to demonstrate respiratory impairment while somatosenory-evoked potentials reflected sensory blockade. Maximal depression of paO2 was 73.9 with and 55.0 mmHg without beta-FNA, while paCO2 rose to 44.7 without and to 35.0 mmHg with beta-FNA (p < 0.005). In the evoked potential, maximal depression was 39.1% with and 92.7% without beta-FNA (p < 0.005). Naltrindole reversed residual hypoxia, however, not hypercarbia or amplitude reduction of the evoked potential. For regulation of paO2, a mu-delta-receptor interaction is postulated while paCO2 and sensory blockade are affected solely by the opioid mu-site.
Latasch
Leo
L
Department of Anesthesiology and Pain Therapy, Krankenhaus Nordwest, Frankfurt/Main, Germany. RockDoc@compuserve.com
Freye
Enno
E
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D017409:Sufentanil / Q000494:pharmacology*
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009271:Naltrexone; C024524:beta-funaltrexamine; D017409:Sufentanil; C055382:naltrindole; D010100:Oxygen