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Antinociceptive and Gastrointestinal Effects of Mu/Kappa Opioid Mixtures in Rats
Author(s) -
Minervini Vanessa,
Osteicoechea Daniela C,
France Charles P
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb607
Subject(s) - morphine , opioid , κ opioid receptor , pharmacology , nociception , agonist , analgesic , potency , chemistry , medicine , receptor , biochemistry , in vitro
Prescription opioids (mu receptor agonists) are commonly used to treat moderate to severe pain despite well‐documented adverse effects (e.g., constipation, abuse). Kappa opioid receptor agonists also have antinociceptive and adverse effects but might be useful for treating pain in drug mixtures. The use of smaller doses in mixtures might reduce or avoid adverse effects that occur with larger doses of either drug given alone. This study evaluated the kappa opioid receptor agonist spiradoline, the mu opioid receptor agonist morphine, and spiradoline:morphine mixtures (in 3:1, 1:1, 1:3, and 1:10 ratios) for their effects on antinociception and gastrointestinal (GI) motility to test the hypothesis that mixtures selectively enhance antinociceptive effects. Tail withdrawal latency from 50°C water was used to assay antinociception in one group of 8 male Sprague Dawley rats, and fecal output (count) was used to assay GI motility in another group of 8 male Sprague Dawley rats. Drugs were given i.p., with tests separated by at least 5 days. Spiradoline (3.2–32 mg/kg) and morphine (1.78–17.8 mg/kg) dose‐dependently increased tail withdrawal latency to a maximum of 20 sec; morphine (1–10 mg/kg) dose‐dependently decreased fecal count from 12 to less than 2 pellets. Spiradoline:morphine in 3:1 and 1:1 ratios had additive antinociceptive effects. The potency of morphine for antinociceptive effects was increased by spiradoline:morphine in 1:3 and 1:10 ratios (greater than predicted additivity). Conversely, in no instances was the potency of morphine increased for effects on GI motility. The potency of morphine to inhibit GI motility was either unchanged (e.g., 1:10) or decreased (e.g., 3:1) by spiradoline:morphine mixtures. Overall, spiradoline:morphine mixtures selectively reduce the dose of morphine needed to produce antinociceptive (therapeutic) effects. It remains to be determined whether spiradoline:morphine mixtures have other adverse effects (abuse, respiratory depression, and dysphoria) and whether interactions between spiradoline and morphine on these outcomes might be related to the ratio of each drug in mixtures. Support or Funding Information This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .