Continuous administration of the 5-hydroxytryptamine1a agonist (3-chloro-4-fluoro-phenyl)-[4-fluor-4-{[(5-methylpyridin-2-ylmethyl)- amino]-methyl}piperidin-1-yl]-methadone (F 13640) attenuates allodynia-like behavior in a rat model of trigeminal neuropathic pain

Kristof Deseure, Wouter Koek, Hugo Adriaensen, Francis C. Colpaert

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)- amino]-methyl}piperidin-1-yl]-methadone (F 13640) is a recently discovered high-efficacy 5-hydroxytryptamine (HT)1A receptor agonist that produces central analgesia through the neuroadaptive mechanisms of inverse tolerance and cooperation. In a rat model of trigeminal neuropathic pain, the chronic constriction injury of the infraorbital nerve causes allodynia-like behavior that develops within 2 weeks and remains stable thereafter. We report that early after surgery, during which time allodynia develops, the continuous 2-week infusion of 0.63 mg/day F 13640 inhibited the allodynia-like behavior, whereas 5 mg/day morphine showed no significant effect. When F 13640 infusion was initiated late after surgery, when allodynia was well established, it produced an antiallodynic effect that was apparent during the entire infusion period. In contrast, morphine infusion caused an initially marked antiallodynic effect to which tolerance developed within the 2-week infusion period. The GABA-B receptor agonist baclofen (1.06 mg/day) that has a recognized usefulness in the treatment of trigeminal neuralgia, demonstrated effectiveness in both conditions. The data are consistent with a theory of nociceptive signal transduction, as well as with previous data, in demonstrating the neuroadaptive mechanisms of inverse tolerance and cooperation. That is, in contrast with morphine, the antiallodynic effect induced by 5-HT1A receptor activation does not decay, but, if anything, grows with chronicity. Also, 5-HT1A receptor activation seemed to cooperate with nociceptive stimulation in, paradoxically, inducing an antiallodynic effect. The data presented here suggest that F 13640 may perhaps offer a lasting treatment of trigeminal neuralgia.

Original languageEnglish (US)
Pages (from-to)505-514
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume306
Issue number2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Continuous administration of the 5-hydroxytryptamine<sub>1a</sub> agonist (3-chloro-4-fluoro-phenyl)-[4-fluor-4-{[(5-methylpyridin-2-ylmethyl)- amino]-methyl}piperidin-1-yl]-methadone (F 13640) attenuates allodynia-like behavior in a rat model of trigeminal neuropathic pain'. Together they form a unique fingerprint.

  • Cite this