title: Effect of fluvoxamine on sufentanil antinociception and tolerance under chronic intravenous infusion in rats.
abstract: Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), significantly potentiates analgesia when administered in animals together with opioids. The aim of the present study was to investigate the effects of fluvoxamine on sufentanil antinociception and tolerance. Following animal care committee approval, the effects of continuous infusions of fluvoxamine and sufentanil were studied in behavioural tests (hot-plate test, tail-flick test, catalepsy test) in Sprague-Dawley rats with a jugular vein catheter. Saline was administered as a control. The time-effect curves for continuous intravenous sufentanil indicate dose-related antinociception and rapid development of tolerance in the hot-plate and tail-flick tests. Co-administration of fluvoxamine with continuous sufentanil enhances antinociception and attenuates development of tolerance, most clearly seen in the tail-flick test. Fluvoxamine alone and saline were not effective. No animal showed catalepsy. As a side effect we observed a marked loss of body weight. The IC50 values of sufentanil binding with and without fluvoxamine addition are 0.56+/-0.17 nM and 0.3+/-0.15 nM, respectively, indicating no direct effect on the occupancy of sufentanil on the mu-receptor by this serotonin reuptake inhibitor. In conclusion, we were able to show that the combination of an opioid with an SSRI at low doses improves analgesia and decreases development of tolerance in nociceptive tests in rats. The clinical implications of these promising results in an animal model, however, await further investigation.
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, The Leopold-Franzens-University of Innsbruck, Austria. thomas.luger@uibk.ac.at
authors.forename: T J
authors.initials: TJ
authors.lastname: Luger
authors.forename: I H
authors.initials: IH
authors.lastname: Lorenz
authors.forename: C
authors.initials: C
authors.lastname: Grabner-Weiss
authors.forename: A
authors.initials: A
authors.lastname: Schlager
authors.forename: C
authors.initials: C
authors.lastname: Kolbitsch
authors.forename: C
authors.initials: C
authors.lastname: Keller
authors.forename: M
authors.initials: M
authors.lastname: Gassner
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D016666:Fluvoxamine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D017409:Sufentanil / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D016666:Fluvoxamine; D017450:Receptors, Opioid, mu; D017367:Selective Serotonin Reuptake Inhibitors; D017409:Sufentanil