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The antinociceptive effect of trazodone in mice is mediated through both mu-opioid and serotonergic mechanisms.

Abstract
The antinociceptive effects of trazodone (a triazolopyridine derivative with antidepressant activity) and its interaction with various opioid, noradrenaline and serotonin receptor subtypes were evaluated. Mice were tested with a hotplate analgesia meter. Trazodone induced a dose-dependent antinociceptive effect following i.p. administration. The ED(50) for mice in the hotplate assay for trazodone was 24.8 mg/kg (9.8; 67.4; 95% CL). The effect of opioid, adrenergic and serotonergic receptor antagonists was examined as to their ability to block trazodone antinociception. Trazodone-induced antinociception was significantly inhibited by naloxone, beta-FNA and naloxonazine, but not by nor-BNI or naltrindole, implying involvement of mu1- and mu2-opioid mechanisms. When adrenergic and serotonergic antagonists were used, metergoline (p<0.05) but not phentolamine or yohimbine, decreased antinociception elicited by trazodone, implying a clear 5-HT mechanism of antinociception. When trazodone was administered together with various agonists of the opioid receptor subtypes, it significantly potentiated antinociception mediated by mu1- and mu2- opioid receptor subtypes. Summing up these results, we conclude that the antinociceptive effect of trazodone is mainly influenced by the mu1- +mu2-opioid receptor subtype combined with the serotonergic receptor. These results explain the diffuse clinical use of trazodone in the management of some pain syndromes, and in opioid- and alcohol-detoxification programs, but raise questions regarding a possible 'indirect' opioid-dependence induced by trazodone itself.
AuthorsS Schreiber, M M Backer, I Herman, D Shamir, T Boniel, C G Pick
JournalBehavioural brain research (Behav Brain Res) Vol. 114 Issue 1-2 Pg. 51-6 (Sep 2000) ISSN: 0166-4328 [Print] Netherlands
PMID10996046 (Publication Type: Journal Article)
Chemical References
  • Analgesics
  • Narcotic Antagonists
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Receptors, Serotonin
  • Serotonin Uptake Inhibitors
  • Trazodone
Topics
  • Analgesics (administration & dosage, pharmacology)
  • Animals
  • Dose-Response Relationship, Drug
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mice, Inbred ICR
  • Narcotic Antagonists (pharmacology)
  • Pain Measurement (drug effects)
  • Reaction Time (drug effects)
  • Receptors, Opioid, delta (drug effects)
  • Receptors, Opioid, kappa (drug effects)
  • Receptors, Opioid, mu (drug effects)
  • Receptors, Serotonin (drug effects)
  • Selective Serotonin Reuptake Inhibitors (administration & dosage, pharmacology)
  • Trazodone (administration & dosage, pharmacology)

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