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

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.

• Authors: Kristof Deseure, Wouter Koek, Francis C Colpaert, Hugo Adriaensen
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 456 Issue 1-3 Pg. 51-7 (Dec 05 2002) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12450569 (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
• F 13640
• Muscle Relaxants, Central
• Narcotics
• Piperidines
• Pyridines
• Receptors, Serotonin
• Receptors, Serotonin, 5-HT1
• Serotonin Receptor Agonists
• Morphine
• Baclofen

Topics

• 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, 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, prevention & control)