The 5-HT(1A) receptor agonist F 13640 attenuates mechanical allodynia in a rat model of trigeminal neuropathic pain

Eur J Pharmacol. 2002 Dec 5;456(1-3):51-7. doi: 10.1016/s0014-2999(02)02640-7.

Abstract

The effects of acute intraperitoneal injections of the 5-HT(1A) receptor agonists F 13640 [(3-chloro-4-fluoro-phenyl)-[4-fluoro-4-[[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl]piperidin-1-yl]-methadone] and F 13714 [3-chloro-4-fluorophenyl-(4-fluoro-4-[[(5-methyl-6-methylamino-pyridin-2-ylmethyl)-amino]-methyl]-piperidin-1-yl-methanone] were studied in comparison with those of baclofen and morphine on responsiveness to von Frey hair stimulation after chronic constriction injury to the rat's infraorbital nerve (IoN-CCI). Following IoN-CCI, an ipsilateral hyperresponsiveness developed that remained stable in control rats throughout the period of drug testing. F 13640, F 13714, baclofen and morphine dose-dependently decreased the hyperresponsiveness; normalization of the response occurred at doses 0.63, 0.04, 5 and 10 mg/kg, respectively. Confirming earlier data, baclofen's effects further validate IoN-CCI as a model of trigeminal neuralgia. The effects of F 13640 and F 13714 are initial evidence that 5-HT(1A) receptor agonists produce profound analgesia in the IoN-CCI model. The present data extend recent evidence that high-efficacy 5-HT(1A) receptor activation constitutes a new mechanism of central analgesia the spectrum of which may also encompass trigeminal neuropathic pain.

MeSH terms

  • Aminopyridines / pharmacology
  • Animals
  • Baclofen / pharmacology
  • Behavior, Animal / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Morphine / pharmacology
  • Muscle Relaxants, Central / pharmacology
  • Narcotics / pharmacology
  • Pain / physiopathology
  • Pain / prevention & control*
  • Piperidines / pharmacology*
  • Pyridines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists / pharmacology*
  • Stress, Mechanical
  • Trigeminal Neuralgia / physiopathology
  • Trigeminal Neuralgia / prevention & control*

Substances

  • 3-chloro-4-fluorophenyl-(4-fluoro-4-(((5-methyl-6-methylaminopyridin-2-ylmethyl)amino)methyl)piperidin-1-yl)methanone
  • Aminopyridines
  • F 13640
  • Muscle Relaxants, Central
  • Narcotics
  • Piperidines
  • Pyridines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • Morphine
  • Baclofen