title: Additive antinociceptive effects of mixtures of the κ-opioid receptor agonist spiradoline and the cannabinoid receptor agonist CP55940 in rats.
abstract: 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.
authors: Departments of aPharmacology bPsychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors: David R
authors: DR
authors: Maguire
authors: Charles P
authors: CP
authors: France
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006358:Hot Temperature; D008297:Male; D059226:Nociceptive Pain / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*
chemical_list: D000700:Analgesics; D063386:Cannabinoid Receptor Agonists; D003511:Cyclohexanols; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C051272:spiradoline