TY - JOUR
T1 - Additive antinociceptive effects of mixtures of the κ-opioid receptor agonist spiradoline and the cannabinoid receptor agonist CP55940 in rats
AU - Maguire, David R.
AU - France, Charles P.
N1 - Publisher Copyright:
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Pain is a significant clinical problem, and there is a need for pharmacotherapies that are more effective with fewer adverse effects than currently available medications. Cannabinoid receptor agonists enhance the antinociceptive effects of μ-opioid receptor agonists; it is unclear whether they impact the effects of agonists acting at other opioid receptors. κ-Opioid receptor agonists have antinociceptive effects, but their clinical use is precluded by adverse effects; however, their therapeutic potential might be realized if antinociceptive effects could be selectively enhanced. In this study, the antinociceptive effects of the cannabinoid receptor agonist CP55940 and the κ-opioid receptor agonist spiradoline, alone and in combination, were studied in rats (n=7) using a warm water tail-withdrawal procedure. When administered alone, CP55940 (0.032-1.0 mg/kg) and spiradoline (1.0-32.0 mg/kg) increased tail-withdrawal latency, and mixtures of CP55940 and spiradoline (ratios of 1:3, 1:1, and 3:1) produced additive effects. It remains to be determined whether this additive interaction between a κ-opioid receptor agonist and a cannabinoid receptor agonist is selective for antinociception and whether it can be generalized to other drugs.
AB - Pain is a significant clinical problem, and there is a need for pharmacotherapies that are more effective with fewer adverse effects than currently available medications. Cannabinoid receptor agonists enhance the antinociceptive effects of μ-opioid receptor agonists; it is unclear whether they impact the effects of agonists acting at other opioid receptors. κ-Opioid receptor agonists have antinociceptive effects, but their clinical use is precluded by adverse effects; however, their therapeutic potential might be realized if antinociceptive effects could be selectively enhanced. In this study, the antinociceptive effects of the cannabinoid receptor agonist CP55940 and the κ-opioid receptor agonist spiradoline, alone and in combination, were studied in rats (n=7) using a warm water tail-withdrawal procedure. When administered alone, CP55940 (0.032-1.0 mg/kg) and spiradoline (1.0-32.0 mg/kg) increased tail-withdrawal latency, and mixtures of CP55940 and spiradoline (ratios of 1:3, 1:1, and 3:1) produced additive effects. It remains to be determined whether this additive interaction between a κ-opioid receptor agonist and a cannabinoid receptor agonist is selective for antinociception and whether it can be generalized to other drugs.
KW - Antinociception
KW - Cannabinoid receptor agonist
KW - Drug-drug interactions
KW - Rat
KW - Thermal nociception
KW - κ-opioid receptor agonist
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U2 - 10.1097/FBP.0000000000000184
DO - 10.1097/FBP.0000000000000184
M3 - Article
C2 - 26292184
AN - SCOPUS:84952690870
SN - 0955-8810
VL - 27
SP - 69
EP - 72
JO - Behavioural pharmacology
JF - Behavioural pharmacology
IS - 1
ER -