title: Potentiation of morphine analgesia by adjuvant activation of 5-HT7 receptors.
abstract: Spinal blockade of 5-HT7 receptors has been reported to inhibit the antinociceptive effect of opioids. In this study, we found that subcutaneous administration of the selective 5-HT7 receptor agonist E-55888 (10 mg/kg) or the antagonist SB-258719 (5 mg/kg) exerted no effect on the tail-flick test in mice. However, E-55888, but not SB-258719, increased (2.6-fold) the analgesic potency of oral morphine. The potentiating effect exerted by E-55888 was prevented by SB-258719. A pharmacokinetic interaction was discarded as morphine plasma and brain concentrations were not significantly modified when co-administered with E-55888. These results reinforce the involvement of 5-HT7 receptors in opioid analgesia and point to a potential use of 5-HT7 receptor agonists as adjuvants of opioid analgesia.
authors.affiliation: Department of Pharmacology, Drug Discovery and Preclinical Development, Esteve, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Brenchat
authors.forename: Miriam
authors.initials: M
authors.lastname: Ejarque
authors.forename: Daniel
authors.initials: D
authors.lastname: Zamanillo
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Vela
authors.forename: Luz
authors.initials: L
authors.lastname: Romero
mesh_terms: D000698:Analgesia / Q000379:methods; D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009020:Morphine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D010880:Piperidines; D011720:Pyrazoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C111309:3,N-dimethyl-N-(1-methyl-3-(4-methylpiperidin-1-yl)propyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C540144:dimethyl-(2-(3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)ethyl)amine dihydrochloride; C104425:serotonin 7 receptor