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Effects of the combined continuous administration of morphine and the high-efficacy 5-HT1A agonist, F 13640 in a rat model of trigeminal neuropathic pain.

Abstract
F 13640 is a recently discovered high-efficacy 5-HT1A receptor agonist that has demonstrated robust anti-allodynic efficacy in a rat model of trigeminal neuropathic pain upon acute and continuous administration. In this model, continuous morphine infusion (5 mg/day) was shown to be effective during the first week of its administration but became almost completely ineffective by the end of the second week; F 13640's effectiveness (0.63 mg/day) remained unchanged during two weeks. Here, we examined the effects of combining F 13640 infusion with that of morphine. During the first week, the combination of the two agents produced a magnitude of effect that was similar to that of morphine when given alone and larger than that of F 13640 alone. During the second week, the combination produced an effect that was similar to that of F 13640 alone, and more effective than that of morphine alone. The latter data suggest that the 5-HT1A agonist, F 13640, inhibits the development of tolerance to morphine in this model. However, it is also possible that little, if any, interaction occurred between the different mechanisms initiated by opioid and 5-HT1A receptor activation, and that the anti-allodynic effect that remained by the end of the two-week treatment period is due solely to 5-HT1A receptor activation. The stable effects of F 13640 during the second week of treatment surpassed those of morphine and were not improved by the addition of morphine to F 13640.
AuthorsKristof R Deseure, Hugo F Adriaensen, Francis C Colpaert
JournalEuropean journal of pain (London, England) (Eur J Pain) Vol. 8 Issue 6 Pg. 547-54 (Dec 2004) ISSN: 1090-3801 [Print] England
PMID15531223 (Publication Type: Journal Article)
Chemical References
  • 3-chloro-4-fluorophenyl-(4-fluoro-4-(((5-methyl-6-methylaminopyridin-2-ylmethyl)amino)methyl)piperidin-1-yl)methanone
  • Aminopyridines
  • Analgesics, Opioid
  • F 13640
  • Piperidines
  • Pyridines
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • Morphine
Topics
  • Aminopyridines (pharmacology)
  • Analgesics, Opioid (therapeutic use)
  • Animals
  • Behavior, Animal (drug effects)
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Drug Tolerance
  • Infusion Pumps, Implantable
  • Male
  • Morphine (therapeutic use)
  • Pain Measurement (drug effects)
  • Physical Stimulation
  • Piperidines (pharmacology, therapeutic use)
  • Pyridines (therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A (drug effects)
  • Serotonin Receptor Agonists (therapeutic use)
  • Trigeminal Neuralgia (drug therapy)

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