Sufentanil-related respiratory depression and antinociception in the dog. Mediation by different receptor types.

Abstract

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.

• Authors: Leo Latasch, Enno Freye
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 52 Issue 12 Pg. 870-6 ( 2002) ISSN: 0004-4172 [Print] Germany
• PMID: 12572526 (Publication Type: Journal Article)

Chemical References

• Analgesics, Opioid
• Narcotic Antagonists
• Receptors, Opioid, delta
• Receptors, Opioid, mu
• Naltrexone
• beta-funaltrexamine
• Sufentanil
• naltrindole
• Oxygen

Topics

• Analgesics, Opioid (pharmacology)
• Animals
• Blood Gas Analysis
• Depression, Chemical
• Dogs
• Dose-Response Relationship, Drug
• Evoked Potentials (drug effects)
• Injections, Intraventricular
• Male
• Naltrexone (analogs & derivatives, pharmacology)
• Narcotic Antagonists (pharmacology)
• Neurons, Afferent (drug effects)
• Oxygen (blood)
• Oxygen Consumption (drug effects)
• Receptors, Opioid, delta (drug effects)
• Receptors, Opioid, mu (antagonists & inhibitors)
• Sufentanil (pharmacology)