FR143166 attenuates spinal pain transmission through activation of the serotonergic system.

Abstract

We investigated the antinociceptive effect of 1-(4-fluorophenyl)-3-methyl-5-[4-(methylsulfinyl)phenyl]pyrazole (FR143166) in the tail-pinch test in mice. The p.o. and i.t. injection of FR143166 exerted dose-dependent antinociceptive actions with ED(50) values of 24 mg/kg and 15 micro g/mouse, respectively. However, i.c.v. injection of FR143166 at a maximum dose of 128 micro g/mouse did not show any antinociceptive effect. The antinociceptive effect of FR143166 injected i.t. was abolished by co-administration of the nonselective serotonin (5-hydroxytryptamine, 5-HT) receptor antagonist, methysergide, but not by the adrenoceptor antagonists, phentolamine and propranolol. Moreover, the effect of FR143166 was also reversed by the 5-HT(2A) receptor antagonist, ketanserin, and the 5-HT(3) receptor antagonist, MDL-72222 (3-tropanyl-3,5-dichlorobenzoate). The effect of FR143166 was attenuated by p-chlorophenylalanine, but not by 6-hydroxydopamine plus nomifensine pretreatment. These results suggest that the descending serotonergic system, especially spinal 5-HT(2A) and 5-HT(3) receptors, is involved in the antinociceptive activity of spinally administered FR143166 on noxious mechanical stimuli.

• Authors: Takehiro Ochi, Yoshitaka Ohkubo, Seitaro Mutoh
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 452 Issue 3 Pg. 319-24 (Oct 11 2002) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12359273 (Publication Type: Journal Article)

Chemical References

• 1-(4-fluorophenyl)-3-methyl-5-(4-(methylsulfinyl)phenyl)pyrazole
• Analgesics
• Pyrazoles
• Receptors, Serotonin
• Serotonin

Topics

• Analgesics (chemistry, pharmacology)
• Animals
• Male
• Mice
• Pain Measurement (drug effects, methods)
• Pyrazoles (chemistry, pharmacology)
• Receptors, Serotonin (metabolism)
• Serotonin (metabolism)
• Spinal Cord (drug effects, metabolism)