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Co-administration of sub-antinociceptive doses of oxycodone and morphine produces marked antinociceptive synergy with reduced CNS side-effects in rats
- Source :
- ResearcherID
- Publication Year :
- 2000
-
Abstract
- Oxycodone and morphine are structurally related, strong opioid analgesics, commonly used to treat moderate to severe pain in humans. Although it is well-established that morphine is a mu-opioid agonist, this is not the case for oxycodone. Instead, our recent studies have shown that oxycodone appears to be a kappa-opioid agonist (Ross and Smith, 1997). In the current study, we now show that co-administration of sub-antinociceptive doses of oxycodone (putative kappa-opioid agonist) with morphine (mu-opioid agonist) to rats by both the intracerebroventricular and by systemic routes (intraperitoneal and subcutaneous), results in markedly increased (synergistic) levels of antinociception. Behaviourally, rats co-administered sub-antinociceptive doses of oxycodone and morphine were similar to control rats dosed with saline, whereas rats that received equi-potent doses of either opioid alone, were markedly sedated. These results suggest that co-administration of sub-analgesic doses of oxycodone and morphine to patients may provide excellent pain relief with a reduction in opioid-related CNS side-effects. Controlled clinical trials in appropriate patient populations are required to evaluate this possibility.(1)
- Subjects :
- Agonist
Central Nervous System
Male
medicine.drug_class
Injections, Subcutaneous
Pharmacology
Rats, Sprague-Dawley
medicine
Animals
Injections, Intraventricular
Behavior, Animal
Dose-Response Relationship, Drug
Morphine
business.industry
Codeine
Nociceptors
Drug Synergism
Rats
Analgesics, Opioid
Dose–response relationship
Drug Combinations
Anesthesiology and Pain Medicine
Nociception
Neurology
Opioid
Nociceptor
Neurology (clinical)
business
Oxycodone
Injections, Intraperitoneal
medicine.drug
Subjects
Details
- ISSN :
- 03043959
- Volume :
- 84
- Issue :
- 2-3
- Database :
- OpenAIRE
- Journal :
- Pain
- Accession number :
- edsair.doi.dedup.....9b7587a555585458ababdaceee5ad564